Investigating the effects of dietary folic acid on sperm count, DNA damage and mutation in Balb/c mice

The cytokinesis-block micronucleus cytome (CBMN-Cyt) assay was originally developed as an ideal system for measuring DNA damage, cytostasis and cytotoxicity. The objective of the present study is to simultaneously evaluate the background levels of micronuclei (MN), nucleoplasmic bridges (NPBs), nuclear buds (NBUDs), cell death (necrosis or apoptosis) and nuclear division index (NDI) in the peripheral blood lymphocytes of non-occupationally exposed, healthy subjects living in the city of Kayseri in Turkey. We used the CBMN-Cyt assay, taking into account factors - age, gender, and smoking habits - that might affect MN frequency and also other CBMN-Cyt assay parameters. Ninety-six healthy subjects (48 female and 48 male) were selected with ages varying between 21 and 60 years. The parameters, except for the number of binucleated (BN) cells with NPBs, showed no statistically significant difference between smokers and non-smokers. There were significant differences between female and male groups in MN frequency (higher in females) and in the number of NPBs (lower in females), while the other parameters were not significantly different between genders. The correlations between years of age and MN frequency, number of NPBs and the frequency of necrotic cells were statistically significant, while the correlations between the years of age and the other parameters were not. The results of the correlation analysis between years of smoking and MN frequency were positive, although no statistically significant correlation was found between the years of smoking and the other parameters. Among the smokers, no correlation was found either between the pack-years of smoking and the parameters assessed in this group. The results of the present study provide evidence of increasing MN frequency, number of NPBs and frequency of necrotic cells with increasing age in the peripheral blood lymphocytes of healthy individuals and influencing MN frequency and number of NPBs by gender.     

A survey on the cytogenetic status of the Croatian general population by use of the cytokinesis-block micronucleus assay

The cytokinesis-block micronucleus assay (CBMN) was used to assess the variability and determine possible influences of external and internal factors on the background levels of cytogenetic damage in peripheral blood lymphocytes (PBL) of 50 healthy volunteers selected at random from the general population of Croatia. The mean MN frequency for all subjects was 4.74+/-0.31 per 1000 cells and the mean cytokinesis-block proliferation index (CBPI) was 1.82+/-0.01. The mean frequency of nucleoplasmic bridges (NPB) for all subjects was 0.06+/-0.04 and of nuclear buds (NB) 0.12+/-0.05. The canonical correlation analyses indicate a positive non-significant correlation between the MN frequency and age, gender and smoking habits. Results of factor structure and canonical weights showed that age and gender rather than smoking habits control the incidence of MN in PBL of healthy volunteers. The lowest median value of MN was observed in subjects younger than 30 years (both smoking and non-smoking). Generally, non-smokers had lower median values of MN compared to smokers. In non-smokers, males showed lower micronucleus incidence than females. Within the non-smokers smaller differences in the median values of MN between subgroups (male and female; age subgroups) were observed. Among smokers, females had a two-fold higher median value of MN frequency than males, but this difference was not significant (p=0.2643, Mann-Whitney U test). Canonical correlation analyses indicate a strong and significant correlation between cell proliferation parameters (M1-M4 and CBPI) and age, gender and smoking habits. The most sensitive parameters were M3 and M4. Age had the strongest effect on M3, while M4 was highly influenced by smoking habits. Gender had an equal non-significant effect on both parameters. The usefulness of the new criteria for the cytokinesis-block MN assay measuring DNA damage as a sensitive biomarker in biomonitoring studies is confirmed.     

Factors contributing to chromosome damage in lymphocytes of cigarette smokers

Cigarette smoking is generally believed to be responsible for a substantial number of human health problems. However, the causal relationship between smoking, the induction of biological effects and the extent of health problems among smokers have not been fully documented. Using the recently developed lymphocyte micronucleus (MN) assay, we have evaluated the chromosome aberration frequencies in 67 cigarette smokers and 59 matched non-smoking control subjects. We found that the mean MN frequency (per 100 cells) in the smokers was slightly higher than that found in the non-smokers (0.71 +/- 0.23 and 0.58 +/- 0.05 respectively; p less than 0.08). Factors which contribute to the expression of chromosome aberrations were also investigated. A significant age-dependent increase in MN frequencies was observed in both groups (p less than 0.05). Linear regression analysis showed that the age-dependent effects among smokers (r = 0.54; p less than 0.02) was further enhanced by cigarette consumption (r = 0.62; p less than 0.005). Consumption of low potency 'one-a-day' type multivitamins had no effect on MN frequencies in either sex of non-smokers and in the 1 male smoker who took multivitamins but vitamin intake consistently reduced the MN frequencies among female smokers. Using a challenge assay, fidelity of DNA repair was evaluated. Lymphocytes from both smokers and non-smokers were irradiated with single doses of 0 or 100 cGy of X-rays or with double doses of 100 cGy of X-rays each separated by 15 or 60 min (100/15 or 100/60). Chromosome translocation frequencies were consistently higher after irradiation in lymphocytes from smokers than in those from non-smokers. Statistically significant differences were detected when the cells were irradiated with the double doses of 100 cGy X-rays each separated by 60 min (p less than 0.05). These data suggest that lymphocytes from smokers made more mistakes in the repair of DNA damage than cells from non-smokers. Our studies provide new insights into the genotoxic effects of cigarette smoke and new information which may be useful for understanding the mechanisms for induction of health problems from smoking.     

Effect of smoking habit on the frequency of micronuclei in human lymphocytes: results from the Human MicroNucleus project

The effect of tobacco smoking on the frequency of micronuclei (MN) in human lymphocytes has been the object of many population studies. In most reports, the results were unexpectedly negative, and in many instances smokers had lower frequencies of MN than non-smokers. A pooled re-analysis of 24 databases from the HUMN international collaborative project has been performed with the aim of understanding the impact of smoking habits on MN frequency. The complete database included 5710 subjects, with 3501 non-smokers, 1409 current smokers, and 800 former smokers, among subjects in occupational and environmental surveys. The overall result of the re-analysis confirmed the small decrease of MN frequencies in current smokers (frequency ratio (FR) = 0.97, 95% confidence interval (CI) = 0.93-1.01) and in former smokers (FR = 0.96, 95% CI = 0.91-1.01), when compared to non-smokers. MN frequency was not influenced by the number of cigarettes smoked per day among subjects occupationally exposed to genotoxic agents, whereas a typical U-shaped curve is observed for non-exposed smokers, showing a significant increase of MN frequency in individuals smoking 30 cigarettes or more per day (FR = 1.59, 95% CI = 1.35-1.88). This analysis confirmed that smokers do not experience an overall increase in MN frequency, although when the interaction with occupational exposure is taken into account, heavy smokers were the only group showing a significant increase in genotoxic damage as measured by the micronucleus assay in lymphocytes. From these results some general recommendations for the design of biomonitoring studies involving smokers can be formulated. Quantitative data about smoking habit should always be collected because, in the absence of such data, the simple comparison of smokers versus non-smokers could be misleading. The sub-group of heavy smokers (> or =30 cigarettes per day) should be specifically evaluated whenever it is large enough to satisfy statistical requirements. The presence of an interaction between smoking habit and occupational exposure to genotoxic agents should be always tested.     

Micronuclei in blood lymphocytes and genetic polymorphism for GSTM1, GSTT1 and NAT2 in pesticide-exposed greenhouse workers.

The frequency of micronuclei (MN) in cultured peripheral lymphocytes was used as a biomarker of genotoxic effects in 34 Italian pesticide-exposed greenhouse workers and 33 unexposed referents matched with the exposed workers for age and smoking habits. The possible influence of the genetic polymorphisms of xenobiotic metabolizing enzymes glutathione S-transferase M1 (GSTM1), T1 (GSTT1), and N-acetyltransferase 2 (NAT2) was also evaluated. To restrict the analysis primarily to cells that have divided once in vitro, MN were scored only in cells showing label after a 42-h incubation with bromodeoxyuridine (BrdU), as detected by immunofluorescence (anti-BrdU technique). Two different concentrations of BrdU (0.5 and 1 microg/ml) were compared. Individual frequencies of micronucleated cells (MNCs) obtained with the two concentrations of BrdU significantly correlated with each other (r=0.55, P<0.001). Higher mean MNCs frequencies (per 1000 cells) were detected among exposed smokers (9.0 at 0.5 microg/ml BrdU and 7.8 at 1 microg/ml BrdU) than in smoking referents (6.3 and 5.9, respectively). In multiple regression analysis controlling for age, sex, smoking and genotypes, a significant elevation of MNC frequency (P=0.004 at 1 microg/ml BrdU; P=0.052 at 0.5 microg/ml BrdU) was observed in greenhouse workers with a work history of extensive pesticide spraying (n=17). Increased MNC frequencies were also associated with ageing at 0.5 microg/ml BrdU, with the GSTM1-positive genotype at both 1 (P=0.028) and 0.5 (P=0.056) microg/ml BrdU in all subjects, and with the NAT2 fast acetylator genotype in smokers at 0.5 microg/ml BrdU (P=0.043). The results indicate that MN rates are increased in greenhouse workers, especially in those involved in pesticide spraying. The GSTM1 positive and NAT2 fast genotypes appear to be associated with elevated MNC frequencies, which contradicts with earlier results on elevated chromosomal aberration rates in GSTM1 null smokers and NAT2 slow subjects.     

Application of the micronucleus test to exfoliated epithelial cells from the oral cavity of beedi smokers, a high-risk group for oral cancer

The primary sites for occurrence of oral cancer include the buccal mucosa, tongue, alveolus, palate, lip and the floor of the mouth. In this study, an attempt was made to estimate the cytogenetic damage in different regions of the oral mucosa in people habituated to smoking beedi,which is one of the major forms of tobacco consumption in India and believed to be a major risk factor for oral cancer. By using the micronucleus assay on exfoliated cells from the buccal mucosa, palate and tongue of beedi smokers, we examined an early cellular response to the effect of beedi smoking. A total number of 50 randomly selected male subjects were included in the study. Case and control groups (smokers and non-smokers, respectively) comprised 25 subjects each. The difference in mean micronucleated cell count between cases and controls was significant (P <0.01) for buccal mucosa and palate, but not for tongue. The correlation between age and micronucleus cell count was weak for both cases (r=0.27) and controls (r=0.36).     

Cytogenetic monitoring of a group of Italian floriculturists: no evidence of DNA damage related to pesticide exposure

The induction of sister chromatid exchanges (SCE), structural chromosome aberrations (CA) or micronuclei (MN) was investigated in peripheral lymphocytes of a group of Italian floriculturists exposed to a mixture of pesticides. No statistically significant difference in the frequencies of cytogenetic damage was detected between exposed and control subjects. Assessment of the effect of confounding factors indicated that smoking affected both SCE and CA frequencies. Multiple regression analysis showed that in heavy smokers (≥ 20 cigarettes/day), SCE and CA levels increased significantly by 17% and 54%, respectively, as compared to non-smokers.     

Urinary cyclophosphamide excretion and micronuclei frequencies in peripheral lymphocytes and in exfoliated buccal epithelial cells of nurses handling antineoplastics

In this study, urinary cyclophosphamide (CP) excretion rate, as well as micronuclei (MN) in peripheral lymphocytes and in buccal epithelial cells were determined for 26 nurses handling antineoplastics and 14 referents matched for age and sex. In urine samples of 20 out of 25 exposed nurses CP excretion rate was found in a range of 0.02-9.14 microg CP/24 h. Our results of the analyses of CP in urine demonstrates that when the nurses were handling CP (and other antineoplastic drugs) this particular compound was observed in urine. The mean values (+/-SD) of MN frequencies (%) in peripheral lymphocytes from the nurses and controls were 0.61 (+/-0. 32) and 0.28 (+/-0.16), respectively (p<0.01). The mean value (+/-SD) of MN frequency (%) in buccal epithelial cells of nurses was 0.16 (+/-0.19) and also mean MN frequency in buccal epithelial cells for controls was found to be as 0.08 (+/-0.08), (p>0.05). Age, sex and smoking habits have not influenced the parameters analyzed in this study. Handling time of antineoplastics, use of protective equipment and handling frequency of drugs have no effect on urinary and cytogenetic parameters analyzed. No correlation was found between the urinary CP excretion and the cytogenetic findings in nurses. Neither could we find any relationship between two cytogenetic endpoints. Our results have identified the possible genotoxic damage of oncology nurses related to occupational exposure to at least one antineoplastic agent, which is used as a marker for drug handling. As a whole, there is concern that the present handling practices of antineoplastic drugs used in the several hospitals in Ankara will not be sufficient to prevent exposure.     

International study of factors affecting human chromosome translocations

Chromosome translocations in peripheral blood lymphocytes of normal, healthy humans increase with age, but the effects of gender, race, and cigarette smoking on background translocation yields have not been examined systematically. Further, the shape of the relationship between age and translocation frequency (TF) has not been definitively determined. We collected existing data from 16 laboratories in North America, Europe, and Asia on TFs measured in peripheral blood lymphocytes by fluorescence in situ hybridization whole chromosome painting among 1933 individuals. In Poisson regression models, age, ranging from newborns (cord blood) to 85 years, was strongly associated with TF and this relationship showed significant upward curvature at older ages versus a linear relationship (p < 0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio (RR) = 1.19, 95% confidence interval (CI), 1.09–1.30) and smoking modified the effect of age on TFs with a steeper age-related increase among ever smokers compared to non-smokers (p < 0.001). TFs did not differ by gender. Interpreting an independent effect of race was difficult owing to laboratory variation. Our study is three times larger than any pooled effort to date, confirming a suspected curvilinear relationship of TF with age. The significant effect of cigarette smoking has not been observed with previous pooled studies of TF in humans. Our data provide stable estimates of background TF by age, gender, race, and smoking status and suggest an acceleration of chromosome damage above age 60 and among those with a history of smoking cigarettes.     

Spontaneous frequency of micronuclei in peripheral blood lymphocytes of Kiev residents]

The level of micronuclei in the peripheral blood lymphocytes of Kyiv residents and its dependence on age, sex and smoking status were studied. Analysis of lymphocytes of 102 healthy Kyiv residents showed that the spontaneous frequency of micronuclei in individuals at the age of 21 to 67 (mean age of 42.6) was 10.5 +/- 0.5@1000. The frequency of micronuclei depends on individual age and increases by 3% per year, and also depends on smoking habits (the micronucleus frequency in smokers was 1.3 times higher then nonsmokers). There is no dependence of the micronucleus frequency on the sex of persons.     

Chromosome aberrations among cigarette smokers in Colombia

Worldwide, the annual morbimortality caused by cigarette smoking is a major public health concern. In Colombia, up to 33% of the adult population has smoked at some point in life, raising important national issues on the disease burden from tobacco. The aim of this study was to establish whether cigarette smoking increases the frequency of chromosome aberrations (CA) in peripheral blood lymphocytes of smokers (n = 52) compared with non-smokers (n = 52) in Popayán, Colombia. After signing a consent form, volunteers provided a blood sample (20 ml) to establish cell cultures at 52 h. For CA analysis, 100 complete metaphase cells from each subject were evaluated. The CA frequency was significantly higher in smokers (8.38 +/- 0.61) than in non-smokers (3.13 +/- 0.29), showing the highest number of CA (14.83 +/- 1.01) among heavy smokers (>20 pack-years). Interestingly, light smokers (< or =10 pack-years) also showed a significant increase in CA when compared to non-smokers (6.62 +/- 0.53 versus 3.13 +/- 0.29, P < 0.01, respectively). In addition, a significant positive correlation was found between the frequency of CA and the intensity of smoking in pack-years (R2 = 0.60). Our study indicates that the genotoxic effects in lymphocytes from smokers are most likely caused by cigarette smoke constituents, providing scientific evidence to encourage national campaigns to prevent tobacco consumption.     

A comparative biomonitoring study of populations residing in regions with low and high risk of lung cancer using the chromosome aberration and the micronucleus tests

Chromosome aberration (CA) and micronucleus (MN) tests were performed in peripheral blood lymphocytes from people residing in two districts of Chiang Mai, Thailand, a high-risk area, Saraphi (n=107), where the lung cancer incidence is three-fold higher than in a low-risk area, Chom Thong (n=118). The percentage of cells with CAs was significantly lower in the Saraphi population than in the Chom Thong population (0.47+/-0.91 versus 1.04+/-1.18, P=0.0001) as was the percentage of CAs (0.49+/-0.91 versus 1.08+/-1.21, P<0.0001) and the mitotic indices (1.25+/-0.44 versus 1.33+/-0.33, P=0.025). The frequency of MN in binucleated (BN) cells, however, was significantly higher in the Saraphi population (12.01+/-3.57 versus 9.99+/-3.11, P<0.0001) as was the percentage of BN cells with MN (1.14+/-0.31 versus 0.93+/-0.23, P<0.0001). There was no difference in the nuclear division indices (1.49+/-0.07 versus 1.47+/-0.11, P=0.1759) between the two populations. With regard to the effect of confounding factors, it was found that cigarette smoking influenced both CA and MN frequencies, and that the chewing of fermented tea leaves or betel nuts affected CA and sex affected MN frequencies. An increasing of CA and MN frequencies were seen in smokers and chewers over non-smokers and non-chewers, with CA frequencies being higher in Chom Thong smokers and chewers and MN frequency being higher in Saraphi smokers. However, pesticide exposure and alcohol consumption had no impact on CA and MN frequencies. Due to the conflicting results obtained in the two tests, we cannot make a clear statement regarding the potential effects of the environmental exposures in the two study populations.     

Differential enhancement of sister-chromatid exchange frequencies by alpha-naphthoflavone in cultured lymphocytes from smokers and non-smokers

The sister-chromatid exchange (SCE) frequency was assessed in peripheral lymphocytes from 4 smokers and 8 non-smokers in the absence or presence of alpha-naphthoflavone (ANF) in the culture media. ANF produced a concentration-dependent increase in the frequency of SCEs in smoking individuals. At an ANF concentration of 11 micrograms/ml, average SCE levels were 54% and 13% above the baseline levels in smokers and non-smokers, respectively. The ANF-enhanced increase in the SCE frequency ranged from 3.12 to 5.72 among smokers, and from 0 to 1.96 among the non-smokers. No significant difference in the mean SCE baseline levels between smokers and non-smokers was detected. The mechanism responsible for the enhanced frequency of SCEs in smokers following in vitro exposure to ANF is not clear, but may reflect changes in metabolic activation/deactivation or increased sensitivity to genetic effects of ANF.     

Investigating the genetic instability in the peripheral lymphocytes of 36 untreated lung cancer patients with comet assay and micronucleus assay

The aim of present investigation was to study the genetic instability in peripheral lymphocytes of lung cancer patients. The micronucleus (MN) assay and comet assay were simultaneously used to detect the spontaneous genetic change and ionizing irradiation (IR) induced genetic damage in peripheral lymphocytes from 36 lung cancer patients and 30 controls. In MN assay, the results of both two indicators, micronucleated cell frequency (MCF) and micronucleus frequency (MNF), indicated that the average values of MCF, MNF and IR-induced MCF, MNF of lung cancer patients were 9.25+/-0.58, 10.17+/-0.72, 66.14+/-2.07 and 75.64+/-2.34 per thousand, respectively, which were significantly higher than those (6.10+/-0.65, 6.60+/-0.74, 60.50+/-1.71 and 67.60+/-2.13 per thousand) of controls (P<0.05 or 0.01). In comet assay, the results of mean tail moment (MTM) and IR-MTM showed 0.84+/-0.07 and 1.09+/-0.11, respectively, which were significantly higher than those (0.60+/-0.05 and 0.70+/-0.10) of controls (P<0.05). However, the difference between lung cancer group and control group for the mean tail length (MTL) and IR-MTL was not significant (P>0.05). The results of present investigation indicated that the genetic instability in peripheral lymphocytes of 36 lung cancer patients was significantly higher than that of controls.     

Increased frequency of micronuclei in B and T8 lymphocytes from smokers

The frequency of micronuclei was measured in peripheral B lymphocytes and some T lymphocyte subpopulations from 5 medium-tar cigarette smokers, and 5 non-smokers with no regular exposure to tobacco smoke. The peripheral lymphocytes were stimulated in vitro with phytohemagglutinin and B lymphocytes and the various T lymphocyte subsets were classified by a recently developed MAC (Morphology, Antibody, Chromosomes) method which allows the immunologic identification of different cell lineages. An increased frequency of micronuclei was observed in B and especially in the suppressor/cytotoxic T8 lymphocytes from smokers, as compared with non-smoker values. In non-smoker cultures, no differences in the frequency of micronuclei were observed among the different T lymphocyte subsets. In these cultures, B cells tended to have a higher frequency of micronuclei than did T cells. The proportions of B cells and the various T subpopulations among mitotic and interphasic lymphocytes from smokers and non-smokers were also determined. The proportions of B cells and T cell subsets among all mitotic lymphocytes were similar in smokers and non-smokers. Contrarily, a significant decrease in the proportion of T8 lymphocytes among all interphasic lymphocytes was observed in cultures derived from smokers.     

Aging and smoking increase the frequency of sister-chromatid exchanges (SCE) in man

The frequency of SCE was determined in lymphocytes of 88 healthy human subjects, not occupationally exposed to known genotoxic agents, who were uniformly distributed in several classes of age (from 16 to 70 years), including an equal number of smokers and non-smokers, and of males and females. Our results indicate that the frequency of SCE increases linearly with age and that smoking enhances the frequency of SCE independently of age and sex.     

Baseline and therapy-induced chromosome damages in peripheral blood lymphocytes of breast cancer patients assessed by the micronucleus assay

Purpose: Radiotherapy (RT) alone or in combination with chemotherapy (CT) leads nearly always to increase of DNA damage in cancer patients. The purpose of this study was to determine the variability rate and individual sensitivity of breast cancer (BC) patients to the applied RT and RT in combination with CT. Methods: The analysed sample included 30 women with histologically confirmed BC. The frequency of micronuclei (MN) was estimated in peripheral blood lymphocytes (PBL) by using the cytokinesis-block micronucleus (CBMN) assay before the administered therapy and one month later. Results: The mean therapy-induced MN value was significantly higher (p < 0.001) compared with mean baseline MN. Both therapies (RT and combined RT+CT) significantly increased the MN frequency in patients' lymphocytes (p<0.001), but without significant differences in the therapy-induced MN frequency between these two groups (p > 0.05). The administered therapy induced significant difference in cell kinetics (p < 0.05). The results showed a wide range of inter-individual variability in both baseline and the therapy-induced MN frequency. Conclusion: The applied therapies increased the MN frequency in PBL in BC patients, and the presented data indicate absence of synergistic effect of these two therapies. None of the variation factors (age, smoking and therapy type) had influence on the noticed variability.     

Cigarette smokers have decreased lymphocyte and platelet alpha-tocopherol levels and increased excretion of the gamma-tocopherol metabolite gamma-carboxyethyl-hydroxychroman (gamma-CEHC)

Cigarette smoking is associated with increased oxidative stress and increased risk of degenerative disease. As the major lipophilic antioxidant, requirements for vitamin E may be higher in smokers due to increased utilisation. In this observational study we have compared vitamin E status in smokers and non-smokers using a holistic approach by measuring plasma, erythrocyte, lymphocyte and platelet alpha- and gamma-tocopherol, as well as the specific urinary vitamin E metabolites alpha- and gamma-carboxyethyl-hydroxychroman (CEHC). Fifteen smokers (average age 27 years, smoking time 7.5 years) and non-smokers of comparable age, gender and body mass index (BMI) were recruited. Subjects completed a 7-day food diary and on the final day they provided a 24 h urine collection and a 20 ml blood sample for measurement of urinary vitamin E metabolites and total vitamin E in blood components, respectively. No significant differences were found between plasma and erythrocyte alpha- and gamma-tocopherol in smokers and non-smokers. However, smokers had significantly lower alpha-tocopherol (mean+/-SD, 1.34+/-0.31 micromol/g protein compared with 1.94+/-0.54, P = 0.001) and gamma-tocopherol (0.19+/-0.04 micromol/g protein compared with 0.26+/-0.08, P = 0.026) levels in their lymphocytes, as well as significantly lower alpha-tocopherol levels in platelets (1.09+/-0.49 micromol/g protein compared with 1.60+/-0.55, P = 0.014; gamma-tocopherol levels were similar). Interestingly smokers also had significantly higher excretion of the urinary gamma-tocopherol metabolite, gamma-CEHC (0.49+/-0.25mg/g creatinine compared with 0.32+/-0.16, P = 0.036) compared to non-smokers, while their alpha-CEHC (metabolite of alpha-tocopherol) levels were similar. There was no significant difference between plasma ascorbate, urate and F2-isoprostane levels. Therefore in this population of cigarette smokers (mean age 27 years, mean smoking duration 7.5 years), alterations to vitamin E status can be observed even without the more characteristic changes to ascorbate and F2-isoprostanes. We suggest that the measurement of lymphocyte and platelet vitamin E may represent a valuable biomarker of vitamin E status in relation to oxidative stress conditions.     

Oncogenic H-ras induces cyclin B1 expression in a p53-independent manner

Alcohol abuse is a major risk factor for cancer of the upper alimentary tract, the upper respiratory tract, and liver. Chromosome damage is used as early effect biomarker in the surveillance of human exposure to genotoxic carcinogens. In the present study, two genetic markers, namely chromosome aberrations (CAs) and micronuclei (MN), were used to evaluate genetic damage in peripheral lymphocytes from 20 alcoholics, 20 abstinent alcoholics, and 20 controls. Composition of the three groups was fairly similar as regards sex, age and smoking habits. A highly significant increase was observed in the frequencies of CA and MN in lymphocytes of alcoholics as compared both with controls and abstinent alcoholics. However, no correlation was found between the length of alcohol abuse and the frequencies of either biomarkers in alcoholics. CA and MN frequencies in abstinent alcoholics were similar than those in controls.Our data indicate that CA and MN can be two useful biomarkers to assess genetic damage associated with alcohol abuse. They could be included in programs for cancer prevention in alcoholics. Abstinence appears to normalize the frequency of both MN and CA. This could offer therapists another tool to help alcoholics change their lifestyle.     

Sister-chromatid exchanges in lymphocytes from styrene-exposed boat builders

Sister-chromatid exchanges (SCE) were measured in peripheral blood lymphocytes from 40 workers in the boat-building trade. Twenty of these workers were exposed to significant amounts of styrene. The mean air concentration of styrene in the breathing zone of the boat builders was 209 mg/m3 in the 7 exposed current smokers and 230 mg/m3 in the 13 exposed non-smokers. Urinary styrene metabolites were also measured and the mean mandelic acid/creatinine ratios in the exposed, smokers was 275 mg/g, and in the exposed, non-smokers 323 mg/g. The SCE frequency in lymphocytes from the styrene-exposed group did not differ from that in the controls, although smoking significantly induced SCE in these workers.