Inhibitory effects of selenium on the growth of DU-145 human prostate carcinoma cells in vitro

The growth of DU-145 human prostate carcinoma cells is reduced to 50% of control by 1 X 10(-6) M to 2 X 10(-6) M selenium and to 2% of control at 10(-4)M selenium. These cells show greater sensitivity to inhibition of growth or DNA synthesis by selenium than human W1-38 and HeLa cells and mouse mammary tumor cells. It has been shown that selenium inhibits carcinogenesis and reduces the incidence of chemical carcinogen and virus-induced tumors of a variety of organs in animals. Selenium may also inhibit the growth of certain tumor cells of non-human origin. To our knowledge, this is the first study on the effects of selenium on the growth of human tumor cells. From extrapolation, it is deduced that selenium serum levels in humans living in high selenium areas may be as high as 10(-6) M and could be effective in inhibiting the growth of tumor cells in vivo. These findings have implications in the prevention and intervention of prostate cancer in man.     

Gender-dependent effects of selenite on the perfused rat heart: a toxicological study

Gender differences are related to the manner in which the heart responds to chronic and acute stress conditions of physiological and pathological nature. Depending on dose, sodium selenite acts as an antioxidant proven to have beneficial effects in several pathological conditions G. Drasch, J. Schopfer, and G. N. Schrauzer, Selenium/cadmium ratios in human prostates: indicators of prostate cancer risk of smokers and nonsmokers, and relevance to the cancer protective effects of selenium, Biol. Trace Element Res. 103(2), 103-107 (2005); R. G. Kasseroller and G. N. Schrauzer, Treatment of secondary lymphedema of the arm with physical decongestive therapy and sodium selenite: a review, Am. J. Ther. 7(4), 273-279 (2000); G. N. Schrauzer, Anticarcinogenic effects of selenium, Cell. Mol. Life Sci. 57(13-14), 1864-1873 (2000); I. S. Palmer and O. E. Olson, Relative toxicities of selenite and selenate in the drinking water of rats, J. Nutr. 104(3), 306-314 (1974). To date, little is known about the gender-dependent direct effects of toxic doses of selenite on electrophysiology of the cardiovascular system H. A. Schroeder and M. Mitchener, Selenium and tellurium in rats: effect on growth, survival and tumors, J. Nutr. 101(11), 1531-1540 (1971); G. N. Schrauzer, The nutritional significance, metabolism and toxicology of selenomethionine, Adv. Food Nutr. Res. 47, 73-112 (2003). In the present study, the effects of in vitro toxic concentrations of sodium selenite ranging from 10-6 M to 10-3 M were tested on both male and female rat heart preparations. The toxic effects seen in an electrocardiogram and left ventricular pressure were dose and sex dependent at most of the tested concentrations. The present study clearly shows that at toxic doses, stress conditions are induced by selenite, resulting in genderdependent modifications of the heart function. This modification is more pronounced in the contraction cascade of female rats. Males, on the other hand, had been much more affected in excitation-related parameters.     

Protective effects of selenium against cadmium induced hematological disturbances,immunosuppressive, oxidative stress and hepatorenal damage in rats

Cadmium is a non-essential toxic metal used in industrial process, causes severe risk to human health. Selenium (Se) is an essential trace mineral of fundamental importance for human health. Selenium has antioxidant enzymes roles and is needed for the proper function of the immune system. In this study, the protective effects of selenium against cadmium intoxication in rats have been investigated by monitoring some selective cytokines (IL-1β, TNF α, IL-6, IL-10 and IFN-γ), antioxidant enzymes reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and lipid peroxidation malondialdehyde (MDA) as well as some selective biochemical markers of liver and kidney functions. Thirty-two rats were divided into four equal groups; the first group was used as a control. Groups 2–4 were treated with selenium (Se; 0.1 mg/kg BW), cadmium (Cd; 40 mg/L drinking water) and selenium plus cadmium, respectively. Rats were orally administered their relevant doses daily for 30 days. Blood samples were collected from heart puncture at the end of the experiment (30 days) for complete blood picture (CBC) and serum was separated to evaluate the different immunological parameters and biochemical parameters, as well as liver specimens for Cd and Se estimation. Rats in the Cd treated group have a significantly higher hepatic concentration of Cd than in other treated groups. Results revealed that cadmium significantly increased IL-1β, TNF α, IL-6 and IL-10, beside peripheral neutrophils count, while the IFN-γ and lymphocytes were decreased in rat sera. In addition, GSH level, CAT, SOD and GPx activities were significantly decreased while lipid peroxidation (MDA) was increased. Regarding, liver and renal markers, they were significantly increased in the activities of aminotransferases (AST, ALT), urea and creatinine, while total plasma proteins and albumin were significantly decreased. On the other hand, selenium treated group, showed significantly increased IFN-γ, GSH level, CAT, and GPx activities, as well as lymphocyte count while IL-10 was decreased. Selenium in combination with cadmium, significantly improved the elevation of serum IL-1β, IL-6, TNF α, IL-10 and malondialdehyde in addition to enhancing the antioxidant enzyme activities of GSH, CAT, GPx and SOD. Moreover, selenium has ameliorated the cadmium-induced liver and kidney damage by improving hepatic and renal markers. The results of this investigation demonstrated that selenium has the potential to countermeasure the immunosuppressive as well as hepatic and renal oxidative damage induced by cadmium in rats; selenium has shown promising effects against Cd toxicity.     

Biochemical and morphological characteristics of selenite-induced apoptosis in human hepatoma hep G2 cells

Selenium is a cellular growth inhibitor in many mammary tumor cells. To comprehend the mechanism for the selenium-induced cell death, we examined the effects of sodium selenite, which has been one of the most extensively investigated selenium compounds, in human hepatoma Hep G2 cells. Cell viability gradually decreased after treatment with sodium selenite within the concentration range of 10–50 μM. Low (10 μM) selenite has shown a high-percentage laddering pattern compared to the high (25 μM) cytotoxic selenium concentration in agarose gel electrophoresis. G₂M-phase enrichment was also concentration dependent. The most consistent transmission electron microscopic finding was the existence of large lysosomes. Based on these data, we hypothesize that sodium selenite predominantly shows its apoptotic effect over hydrogen selenite accumulation.     

Differential effects on growth, cell cycle arrest, and induction of apoptosis by resveratrol in human prostate cancer cell lines.

Epidemiologic studies have suggested that nutrition plays an important role in carcinogenesis and that 30% of cancer morbidity and mortality can potentially be prevented with proper adjustment of diets. Resveratrol, a polyphenol present in red wines and a variety of human foods, has recently been reported to exhibit chemopreventive properties when tested in a mouse skin cancer model system. In this study, we investigated the effects of resveratrol on growth, induction of apoptosis, and modulation of prostate-specific gene expression using cultured prostate cancer cells that mimic the initial (hormone-sensitive) and advanced (hormone-refractory) stages of prostate carcinoma. Androgen-responsive LNCaP and androgen-nonresponsive DU-145, PC-3, and JCA-1 human prostate cancer cells were cultured with different concentrations of resveratrol (2. 5 x 10(-5)-10(-7) M). Cell growth, cell cycle distribution, and apoptosis were determined. Addition of 2.5 x 10(-5) M resveratrol led to a substantial decrease in growth of LNCaP and in PC-3 and DU-145 cells, but only had a modest inhibitory effect on proliferation of JCA-1 cells. Flow cytometric analysis showed resveratrol to partially disrupt G1/S transition in all three androgen-nonresponsive cell lines, but had no effect in the androgen-responsive LNCaP cells. In difference to the androgen-nonresponsive prostate cancer cells however, resveratrol causes a significant percentage of LNCaP cells to undergo apoptosis and significantly lowers both intracellular and secreted prostate-specific antigen (PSA) levels without affecting the expression of the androgen receptor (AR). These results suggest that resveratrol negatively modulates prostate cancer cell growth, by affecting mitogenesis as well as inducing apoptosis, in a prostate cell-type-specific manner. Resveratrol also regulates PSA gene expression by an AR-independent mechanism.     

v-rasH expression confers hormone-independent in vitro growth to LNCaP prostate carcinoma cells

The LNCaP human prostate cancer cell line is dependent on androgen for in vitro growth. To discover genes that may be responsible for progression of prostate cancer from hormone dependence to hormone independence, we transfected LNCaP cells with expression vectors that contained either the v-rasH or c-rasH gene under the control of the cadmium (Cd2+)-inducible human metallothionein-IIA promoter. Numerous derivative cell lines were isolated which manifested inducible expression of rasH p21 protein when the cells were treated with Cd2+. None of the cell lines transfected with c-rasH were found to have an altered growth phenotype. Several derivative cell lines expressing inducible v-rasH manifested hormone-independent growth in culture when treated with 10(-7) M Cd2+ . Cd2+ induction of v-rasH p21 was also shown to increase anchorage-independent colony formation of the v-rasH-expressing cell lines tested. Expression of a dominant mutated oncogene can change the hormone-dependent growth phenotype of prostate cancer cells.     

Selenium mitigates cadmium-induced oxidative stress in tomato (<Emphasis Type="Italic">Solanum lycopersicum</Emphasis> L.) plants by modulating chlorophyll fluorescence,osmolyte accumulation,and antioxidant system

Pot experiments were conducted to investigate the role of selenium in alleviating cadmium stress in Solanum lycopersicum seedlings. Cadmium (150 mg L^?1) treatment caused a significant reduction in growth in terms of height and biomass accumulation and affected chlorophyll pigments, gas exchange parameters, and chlorophyll fluorescence. Selenium (10 μM) application mitigated the adverse effects of cadmium on growth, chlorophyll and carotenoid contents, leaf relative water content, and other physiological attributes. Lipid peroxidation and electrolyte leakage increased because of cadmium treatment and selenium-treated plants exhibited considerable reduction because of the decreased production of hydrogen peroxide in them. Cadmium-treated plants exhibited enhanced activity of antioxidant enzymes that protected cellular structures by neutralizing reactive free radicals. Supplementation of selenium to cadmium-treated plants (Cd + Se) further enhanced the activity of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) by 19.69, 31.68, 33.14, and 54.47%, respectively. Osmolytes, including proline and glycine betaine, increased with selenium application, illustrating their role in improving the osmotic stability of S. lycopersicum under cadmium stress. More importantly, selenium application significantly reduced cadmium uptake. From these results, it is clear that application of selenium alleviates the negative effects of cadmium stress in S. lycopersicum through the modifications of osmolytes and antioxidant enzymes.     

Selenium interactions and toxicity: a review

Selenium is an essential trace element for mammals. Through selenoproteins, this mineral participates in various biological processes such as antioxidant defence, thyroid hormone production, and immune responses. Some reports indicate that a human organism deficient in selenium may be prone to certain diseases. Adverse health effects following selenium overexposure, although very rare, have been found in animals and people. Contrary to selenium, arsenic and cadmium are regarded as toxic elements. Both are environmental and industrial pollutants, and exposure to excessive amounts of arsenic or cadmium can pose a threat to many people’s health, especially those living in polluted regions. Two other elements, vanadium and chromium(III) in trace amounts are believed to play essential physiological functions in mammals. This review summarizes recent studies on selenium interactions with arsenic and cadmium and selenium interactions with vanadium and chromium in mammals. Human studies have demonstrated that selenium may reduce arsenic accumulation in the organism and protect against arsenic-related skin lesions. Selenium was found to antagonise the prooxidant and genotoxic effects of arsenic in rodents and cell cultures. Also, studies on selenium effects against oxidative stress induced by cadmium in various animal tissues produced promising results. Reports suggest that selenium protection against toxicity of arsenic and cadmium is mediated via sequestration of these elements into biologically inert conjugates. Selenium-dependent antioxidant enzymes probably play a secondary role in arsenic and cadmium detoxification. So far, few studies have evaluated selenium effects on chromium(III) and vanadium actions in mammals. Still, they show that selenium may interact with these minerals. Taken together, the recent findings regarding selenium interaction with other elements extend our understanding of selenium biological functions and highlight selenium as a potential countermeasure against toxicity induced by arsenic and cadmium.     

Effect of Sodium Selenite on Gene Expression of SELF,SELW, and TGR Selenoproteins in Adenocarcinoma Cells of the Human Prostate

Selenium is an essential trace element, the deficiency of which leads to the development of several serious diseases, including male infertility, prostate cancer, etc. It has been shown that oxidative stress contributes to the progression of prostate cancer, and antioxidants such as selenium and vitamin E can significantly reduce the risk of this disease. Sodium selenite, one of the selenium compounds that induce the formation of reactive oxygen species, is considered as a potential anticancer agent. The SS concentrations that lead to a decrease in the viability of human prostate adenocarcinoma cells (line Du-145) have been selected, and the effect of sodium selenite on the expression of mRNA of the SELV, SELW, and TGR selenocysteine proteins in these cells has been analyzed.     

Oncogenic transformation of human benign prostate hyperplasia with chronic cadmium exposure

Experimentally, it has been proved that cadmium served as an effective carcinogen and able to induce tumors in rodents in a dose-specific manner. However, systemic evaluation of cadmium exposure for the transformation of prostatic hyperplasia into prostate cancer (PCa) is still unclear. In the present study, an attempt has been made to establish cadmium-induced human prostate carcinogenesis using an in vitro model of BPH cells. Wide range of cadmium concentrations, i.e., 1 nM, 10 nM, 100 nM and 1μM, were chronically exposed to the human BPH cells for transformation into PCa and monitored using cell and molecular biology approaches. After eight weeks of exposure, the cells showed subtle morphological changes and shifts of cell cycle in the G2M phase. Significant increase in expression of prostatic genes AR, PSA, ER-β, and 5αR with increased nuclear localization of AR and pluripotency markers Cmyc, Klf4 indicated the carcinogenic effect of Cd. Further, the BPH cells exposed to Cd showed a substantial increase in the secretion of MMP-2 and MMP-9, influencing migratory potential of the cells along with decreased expression of the p63 protein which further strengthen the progression towards carcinogenesis and aggressive tumor studies. Data from the present study state that Cd exhibited marked invasiveness in BPH cells. These observations established a connecting link of BPH towards PCa pathogenesis. Further, the study will also help in investigating the intricate pathways involved in cancer progression.     

Selenoprotein expression is regulated at multiple levels in prostate cells

Selenium supplementation in a population with low basal blood selenium levels has been reported to decrease the incidence of several cancers including prostate cancer. Based on the clinical findings, it is likely that the antioxidant function of one or more selenoproteins is responsible for the chemopreventive effect, although low molecular weight seleno-compounds have also been posited to selectively induce apoptosis in transformed cells. To address the effects of selenium supplementation on selenoprotein expression in prostate cells, we have undertaken an analysis of antioxidant selenoprotein expression as well as selenium toxicity in non-tumorigenic prostate epithelial cells （RWPE- 1 ） and prostate cancer cells （LNCaP and PC-3）. Our results show that two of the glutathione peroxidase family members （GPX1 and GPX4） are highly induced by supplemental selenium in prostate cancer cells but only slightly induced in RWPE-1 cells. In addition, GPX 1 levels are dramatically lower in PC-3 cells as compared to RWPE- 1 or LNCaP cells. GPX2 protein and mRNA, however, are only detectable in RWPE-1 cells. Of the three selenium compounds tested （sodium selenite, sodium selenate and selenomethionine）, only sodium selenite shows toxicity in a physiological range of selenium concentrations. Notably and in contrast to previous studies, RWPE-1 cells were significantly more sensitive to selenite than either of the prostate cancer cell lines. These results demonstrate that selenoproteins and selenium metabolism are regulated at multiple levels in prostate cells.     

Gender-dependent effects of selenite on the perfused rat heart

Gender differences are related to the manner in which the heart responds to chronic and acute stress conditions of physiological and pathological nature. Depending on dose, sodium selenite acts as an antioxidant proven to have beneficial effects in several pathological conditions G. Drasch, J. Schopfer, and G. N. Schrauzer, Selenium/cadmium ratios in human prostates: indicators of prostate cancer risk of smokers and non-smokers, and relevance to the cancer protective effects of selenium,Biol. Trace Element Res. 103(2), 103–107 (2005); R. G. Kasseroller and G. N. Schrauzer, Treatment of secondary lymphedema of the arm with physical decongestive therapy and sodium selenite: a review,Am. J. Ther. 7(4), 273–279 (2000); G. N. Schrauzer, Anticarcinogenic effects of selenium,Cell. Mol. Life Sci. 57(13–14), 1864–1873 (2000); I. S. Palmer and O. E. Olson, Relative toxicities of selenite and selenate in the drinking water of rats,J. Nutr. 104(3), 306–314 (1974). To date, little is known about the gender-dependent direct effects of toxic doses of selenite on electrophysiology of the cardiovascular system H. A. Schroeder and M. Mitchener, Selenium and tellurium in rats: effect on growth, survival and tumors,J. Nutr. 101(11), 1531–1540 (1971); G. N. Schrauzer, The nutritional significance, metabolism and toxicology of selenomethionine,Adv. Food Nutr. Res. 47, 73–112 (2003). In the present study, the effects of in vitro toxic concentrations of sodium selenite ranging from 10^-6 M to 10^-3 M were tested on both male and female rat heart preparations. The toxic effects seen in an electrocardiogram and left ventricular pressure were dose and sex dependent at most of the tested concentrations. The present study clearly shows that at toxic doses, stress conditions are induced by selenite, resulting in gender-dependent modifications of the heart function. This modification is more pronounced in the contraction cascade of female rats. Males, on the other hand, had been much more affected in excitation-related parameters.     

The genotoxicity of selenium

Selenium at nutritional levels has been shown to have numerous anticarcinogenic or preventative effects against carcinogen-induced breast, colon, liver and skin cancer in animals. Many of these anticarcinogenic effects have been summarized. In addition, numerous mutagenic and antimutagenic effects of selenium compounds have been reported. Some of the selenium compounds frequently tested for mutagenicity are listed in Table 1. Because of the numerous reported anticarcinogenic and preventative effects of selenium, many individuals are supplementing their diets with amounts of selenium that are greater than the recommended daily requirement. Selenium is also used widely in industrial products such as selenium rectifiers, photoelectric batteries, alloys and paints. Because selenium at higher levels is known to be toxic, there should be a greater understanding about its genotoxic as well as its beneficial effect. The object of this review is to summarize experimental evidence both for the antimutagenic and the mutagenic effect of selenium.     

Toxic and cytogenetic effects induced in Allium cepa with low concenrations of Cd and 232th

232Th (7.76 x 10(-7) M) and Cd (0.89 x 10(-8) M) in concentrations which do not exceed officially prescribed standards when entering with water do not increase the frequency of chromosome aberrations in comparison with the control. Such concentrations do not cause toxic effects in plants on the levels of tissues and of the whole organism but they do display their activity on the cell level damaging division spindle. Dependence "cadmium concentration-effect" is not linear for any type of cytogenetical damages. At the concentration of cadmium 0.89 x 10(-7) M its influence on formation of division spindle is weakened and the frequency of chromosome aberrations is reducing in comparison with the control and with the effects induced at lower concentrations of cadmium in solution (0.89 x 10(-8) M). Cadmium in high concentration (5.34 x 10(-5) M) causes significant toxic and mutagenic effects.     

硒对镉胁迫下大球盖菇菌丝生长的影响

选用大球盖菇Stropharia rugosoannulata为试验材料,分析在镉胁迫处理下（2mg/L）添加不同浓度硒（0、6、15、20mg/L）对大球盖菇菌丝生长的影响,初步研究了施加硒对镉胁迫下大球盖菇菌丝生长抑制的缓解效应和作用机制。结果表明：镉对大球盖菇生长速度和生物量具有明显抑制作用,镉造成了大球盖菇渗透调节物质、过氧化氢和丙二醛含量显著增加;添加硒后,镉对大球盖菇菌丝的生长速度、生物量抑制作用均有所改善,且增加了渗透调节物质,促进镉胁迫下大球盖菇渗透调节能力;硒诱导抗氧化酶的活性上调,提高活性氧清除能力,降低了菌丝中丙二醛和过氧化氢的含量,缓解细胞膜过氧化程度,增强了大球盖菇对镉的耐受性。本研究重点探讨外源添加硒对镉胁迫下大球盖菇菌丝生长、生理特性及抗氧化胁迫能力的影响,为进一步研究硒在食用菌抗镉栽培中的应用奠定了一定的理论基础。     

Effect of selenium fertilization on the accumulation of cadmium and lead in rice plants

Background and Aims

The accumulation of cadmium and lead in rice (Oryza sativa L.) grains is a potential threat to human health. In this study, the effect of selenium fertilization on the uptake and translocation of cadmium and lead in rice plants was investigated.

Methods

Rice plants were cultivated using cadmium and lead contaminated soils with selenium addition at three concentrations (0, 0.5 and 1 mg kg^?1). At maturity, plants were harvested, and element concentrations in rice tissues were analyzed by using ICP-MS.

Results

Selenium application significantly increased selenium accumulation in rice grain, and markedly decreased cadmium and lead concentrations in rice tissues. In brown rice grains, selenium application reduced cadmium concentrations by 44.4 %, but had no significant effect on lead accumulation. Selenium application significantly decreased metal mobility in soils, at 0.5 mg kg^?1 treatment, the translocation factor of cadmium and lead from soil to iron plaque decreased by 71 and 33 % respectively.

Conclusions

The mechanism of selenium mitigating of heavy metal accumulation in rice could be decreasing metal bioavailability in soil. Selenium fertilization could be an effective and feasible method to enrich selenium and reduce cadmium levels in brown rice.     

Influence of selenium on the growth of N-nitrosomethylurea-induced mammary tumor cells in culture

Selenium is an essential dietary trace element which has anticancer properties. Among its effects in rats, selenium has been shown to inhibit the development of carcinogen-induced mammary tumors by interfering with the postinitiation, promotion phase of carcinogenesis. We studied the effects of selenium on the growth of rat mammary tumor cells in primary culture. Our objective was to determine whether selenium had any direct influence on cell growth which might explain its influence on tumor development. Rat mammary tumors were induced by N-nitrosomethylurea. Tumor epithelium was prepared by collagenase dispersion and the cells were separated by Ficoll gradient centrifugation. The tumor epithelium was grown in primary culture using a defined serum-free medium. The addition of low concentrations of sodium selenite, less than 1.0 micrograms/ml, stimulated tumor cell proliferation. Protein synthesis and the production of type IV collagen increased within the first hour of exposure, prior to any measurable increase in DNA synthesis. Concentrations of selenite greater than 1.0 micrograms/ml inhibited cell proliferation, the synthesis of protein, and the replication of DNA in a dose-related manner. These studies demonstrated that selenium has the potential to influence the postinitiation phase of rat mammary tumorigenesis by directly altering the growth of tumor cells, possibly through the regulation of protein synthesis.     

Selenium tolerance of yeasts

Selenium tolerance of yeasts widely varies: the growth of some yeasts can be inhibited by a selenium concentration as low as 10(-4) M, whereas others can grow in the presence of 10(-1) M selenium. Homogeneous yeast taxa are characterized by a certain level of selenium tolerance, and heterogeneous taxa show a variable level of tolerance to selenium. In general, ascomycetous yeasts are more tolerant to selenium than basidiomycetous yeasts. Among the ascomycetous yeasts, the genera Dekkera and Schizosaccharomyces exhibited the lowest and the species Candida maltosa, Hanseniaspora valbyensis, Kluyveromyces marxianus, and Yarrowia lipolytica the highest tolerance to selenium. Among the basidiomycetous yeasts, the genera Bullera, Cryptococcus, and Holtermannia showed the lowest and the species Cryptococcus curvatus, Cr. humicola, and Trichosporon spp. the highest tolerance to selenium. The selenium tolerance of yeasts depends on the composition of the growth medium, in particular, on the presence of sulfate, sulfur-containing amino acids, and glutamine in the medium.     

Update on the effects of vitamins A, C, and E and selenium on carcinogenesis

The effects of vitamins A, C, and E and of selenium on carcinogenesis are briefly summarized and updated. These vitamins and minerals were selected because they have been studied extensively in recent years with a variety of carcinogenesis models. The consumption of vitamin A and its precursors (carotenoids) has been negatively correlated with cancer at a number of sites, particularly the lung. Animal investigations on vitamin A involvement in carcinogenesis have generally been of three types: those assessing the effect of vitamin A deficiency, the effect of excess vitamin A, or the effect of supplementation with synthetic analogs of vitamin A. Vitamin A deficiency had no effect on salivary gland carcinogenesis, enhanced urinary bladder, lung, and liver carcinogenesis, and inhibited colon carcinogenesis. Excess of various forms of vitamin A enhanced or inhibited skin tumorigenesis, inhibited mammary carcinogenesis in rats (but not in mice), and carcinogenesis of the forestomach, liver, and urinary bladder (with one model, but not with another), or enhanced or did not influence lung carcinogenesis. Vitamin A analogs have enhanced or inhibited skin tumorigenesis, inhibited salivary gland, mammary, and urinary bladder carcinogenesis, enhanced tracheal and liver carcinogenesis, and either enhanced or inhibited pancreas carcinogenesis, depending upon the model employed. Although retinoids have been shown to inhibit carcinogenesis at many sites, numerous negative studies have been reported and some reports have indicated enhanced carcinogenesis. The most convincing evidence for the involvement of vitamin C in cancer prevention is the ability of ascorbic acid to prevent formation of nitrosamine and of other N-nitroso compounds. In addition vitamin C supplementation was shown to inhibit skin, nose, tracheal, lung, and kidney carcinogenesis, to either not influence or enhance skin, mammary gland, and colon carcinogenesis, and to enhance urinary bladder carcinogenesis, when given as sodium ascorbate, but not when given as ascorbic acid. Like vitamin C, vitamin E can inhibit nitrosation. Vitamin E was shown to inhibit skin, cheek pouch, and forestomach carcinogenesis, to enhance or inhibit colon carcinogenesis, and to have no effect on or to inhibit mammary gland carcinogenesis, depending upon the method of vitamin E administration or the level of dietary selenium or dietary fat. Selenium effects on carcinogenesis have been recently reviewed and the present discussion only updates this area by indicating that enhancement of carcinogenesis by dietary selenium supplements has been observed in the liver, pancreas, and skin.(ABSTRACT TRUNCATED AT 400 WORDS)