Leukocyte 8-oxo-7,8-dihydro-2′-deoxyguanosine and comet assay in epirubicin-treated patients

Epirubicin fights cancer through topoisomerase II inhibition, hence producing DNA strand breaks that finally lead to cell apoptosis. But anthracyclines produce free radicals that may explain their adverse effects. Dexrazoxane—an iron chelator—was proven to decrease free radical production and anthracycline cardiotoxicity.

In this article, we report the concentrations of cellular 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dGuo) relative to 2′-deoxyguanosine (dGuo), and comet assay results from a study including 20 cancer patients treated with epirubicin. Plasma concentrations of vitamins A, E, C and carotenoids are also reported. All data were obtained before and immediately after epirubicin infusion. The ratios of 8-Oxo-dGuo to dGuo were measured in leukocyte DNA by HPLC-coulometry after NaI extraction of nucleic acids. Vitamins A and E and carotenoids were measured by HPLC-spectrophotometry. Vitamin C was measured by HPLC-spectrofluorimetry.

Median 8-oxo-dGuo/dGuo ratios increased significantly from 0.34 to 0.48 lesions per 100,000 bases while per cent of tail DNA increased from 3.47 to 3.94 after chemotherapy 8-Oxo-dGuo/dGuo and per cent of tail DNA medians remained in the normal range. Only vitamin C decreased significantly from 55.4 to 50.3?μM Decreases in vitamins A, E, lutein and zeaxanthin were not significant, but concentrations were below the lower limit of the normal range both before and after chemotherapy. Only the correlation between comet assay results and vitamin C concentrations was significant ( ).

This study shows that cellular DNA is damaged by epirubicin-generated free radicals which produce the mutagenic modified base 8-oxo-dGuo and are responsible for strand breaks. However, strand breaks are created not only by free radicals but also by topoisomerase II inhibition. In a previous study we did not find any significant change in urinary 8-oxo-dGuo excretion after adriamycin treatment. However, 8-oxo-dGuo may have increased at the end of urine collection as DNA repair and subsequent kidney elimination are relatively slow processes. In another study, authors used GC-MS to detect 8-oxo-dGuo in DNA and did not find any change after prolonged adriamycin infusion. Reasons for these apparent discrepancies are discussed.     

Induction of Multidrug Resistance-Associated Protein MRP3 in the Liver of Rats Fed with Docosahexaenoic Acid

To clarify the alternative mechanisms to vitamin E (VE) regulating lipid peroxide accumulation in the liver after docosahexaenoic acid (DHA) ingestion, we examined the relationship between the DHA-induced lipid peroxide formation and induction of the xenobiotic transporters, Ral-binding GTPase-activating protein (RalBP1) and multidrug resistance-associated proteins 1, 2 and 3 (MRP1–3), in the liver of rats fed with DHA. The test diets contained DHA and linoleic acid (LA) (8.7% and 2.1% of total energy, respectively) with different levels of dietary VE (normal and low: 68 and 7.7 mg of alpha-tocopherol equivalent per kg diet, respectively), and the control diet contained LA alone (11.5% of total energy). The rats were fed with these experimental diets for 14 d. The proportions of DHA in the liver, kidney and heart were higher in the DHA-fed groups than in the LA-fed group. The tissue thiobarbituric acid values as an index of lipid peroxidation were also significantly higher in the DHA-fed groups, but the value did not differ between the DHA-fed groups with different VE levels. In the liver, there were no significant differences in the glutathione S-transferase (GST) and aldehyde dehydrogenase (ALDH) activities or in the expression of GST M2, RalBP1, MRP1 and MRP2 mRNA. However, the obvious induction of expression of liver MRP3 mRNA and tendency to produce the protein were recognized after DHA ingestion. This study is the first to report the gene expression of MRP3 by DHA ingestion. There might exist, therefore, some relationship between the DHA intake and MRP3 induction in regulating lipid peroxide accumulation in the liver.     

Annual variations in plasma retinol and alpha-tocopherol levels in gentoo and rockhopper penguins

Blood samples were taken throughout the year from captive gentoo Pygoscelis papua (n = 5) and rockhopper Eudyptes crestatus (n = 10) penguins to measure seasonal variations in retinol and alpha-tocopherol levels. Retinol levels ranged from .58 μg/ml to 1.09 μg/ml and alpha-tocopherol levels from 30.8 μg/ml to 50.7 μg/ml for the gentoo penguins. The rockhopper penguins' retinol levels ranged from .63 μg/ml to 1.14 μg/ml and alpha-tocopherol from 22.3 μg/ml to 40.8 μg/ml. Changes in body mass were used as an indicator of the start and duration of feather moult. Food consumption was recorded daily for the year, and the vitamin A and E intake was calculated. Blood vitamin levels of penguins on a supplemented diet were similar to those in the wild. © 1993 Wiley-Liss, Inc.     

Serum zinc in patients with cystic fibrosis at diagnosis and after one year of therapy

There is no consensus whether zinc (Zn) supplementation is necessary in cystic fibrosis (CF). For assessment of the Zn status, serum Zn concentration is the only easy available method. It is, however age dependent. We compare the serum Zn levels of CF patients with earlier reported normal values. Serum Zn was determined in all new diagnosed CF patients and a second time 1 yr later. Data concerning fat-soluble vitamin status, cholesterol, albumin, pancreatic insufficiency, and genotype were collected. Thirty-two patients, median age of 1.21 yr, were included. Four were pancreatic sufficient. The median Zn concentration at diagnosis was 10.7 μmol/L (5–21.4), with a significant increase 1 yr later (median: 12.1 μmol/L [7,803–16,1]). An association of serum Zn with vitamin A (p<0.03) and with vitamin E (p<0.02) was observed. Compared to age-matched healthy controls, there is no significant difference in serum Zn concentration either at diagnosis or 1 yr later. Although it was demonstrated that steatorrhoea causes Zn loss, the serum Zn concentration in CF is not significantly different from healthy controls. The relation with vitamin A and E points to the increased losses by steatorrhoea. Therefore, Zn supplementation is advised in persisting steatorrhoea.     

Effect of Vitamin B12-Enriched Thraustochytrids on the Population Growth of Rotifers

Newly isolated thraustochytrids showed uptake of vitamin B12 from the culture into the cells. Cultivation of thraustochytrids in a medium containing 1 μg/ml of vitamin B12 greatly increased the contents of vitamin B12 in the cells. Similarly to Schizochytrium limacinum, odd numbered fatty acids decreased in the cells of new isolates cultivated with vitamin B12. Vitamin B12-enriched thraustochytrids, strain mh0186, enhanced the population growth of rotifers fed on the cells as sole feed.     

中国拟青霉属的两个新记录种

报道了国内拟青霉属的两个新记录种 ,即彭氏拟青霉 [Paecilomycespuntonii (Vuillemin)Nannizzi]和马昆德拟青霉 [Paecilomycesmarquandii (Massee)Hughes],经测定其 10 0g干菌丝维生素A含量分别为 2 13g和 3 14g ;维生素E含量分别为 3 4 5g和 4 6 0g。     

植物类胡萝卜素代谢工程与应用

类胡萝卜素是人类所需要的重要营养成分之一,不仅具有抗氧化、预防肿瘤和心血管等疾病的作用,而且还是人体合成维生素A的前体。全球大约有280万～330万学龄前儿童出现维生素缺乏（vitaminAdeficiency,VAD）的临床症状;近2亿儿童处于半缺乏状态。通过对植物类胡萝卜素生物合成途径的解析,以及对参与这一代谢过程的酶及其调控机制的深入了解,目前已经可以通过基因工程在主要农作物中组织特异性地促进类胡萝卜素的合成与积累。从理论上已经可以利用转基因植物来减少VAD的出现。该文简要回顾近年来这一领域的研究进展。     

Changes in the Level of Sialic Acid in Plasma,Brain and Liver of Inherently Scorbutic Rats during Vitamin C and E Deficiencies

The plasma level of sialic acid (NeuAc) in inherently scorbutic [Osteogenic Disorder Shionogi (ODS)] rats was increased by 21 days of vitamin C deficiency and simultaneous vitamins C and E deficiency. The brain content of NeuAc was decreased by deficiencies of these vitamins. The NeuAc level in the liver was not affected significantly by these deficiencies.