Effect of dietary selenium on the interaction between 2-acetylaminofluorene and rat liver DNA in vivo.

Male weanling Charles River CD rats were fed a Torula yeast based selenium-deficient diet or the same diet supplemented with selenium (0.5 ppm), as sodium selenite. Animals fed the basal diet for 3 weeks developed a functional selenium defi ciency as evidenced by an almost total loss of hepatic, sele nium-dependent glutathione peroxidase (glutathione:H2O2 ox idoreductase, EC i .1i .i .9) activity. In contrast, rats fed the selenium-supplemented diet exhibited an increase in glutathi one peroxidase activity during the same interval. There was no difference between selenium-deficient and selenium-supplemented rats with respect to the total amount of 2-acetylaminofluorene covalently bound to liver DNA in viva at i , 4, i 6, 24, 96, or i 68 hr following a single i.p. injection of 2(9-' 4Cjacetylaminofluorene. However, alkaline sucrose gra dient analysis revealed the production of DNA single-strand breaks in the livers of selenium-deficient rats at 4 hr after i.p. injection of 2-acetylammnofluorene(i 0 mg/kg). These lesions were apparently repaired at 24 hr after injection of the carcin ogen. Under the same conditions, 2-acetylaminofluorene failed to produce evidence of DNA damage in the livers of selenium supplemented rats. Administration of 2-acetylammnofluoreneat the dose of 20 mg/kg resulted in extensive degradation of hepatic DNA in both groups of rats. Repair of this damage occurred at 48 to 72 hr after carcinogen administration and was unaffected by the selenium status of the animals. The possible involvement of peroxidative processes in 2acetylammnofluorene-mnducedDNA damage was investigated by measuring the hepatic malondialdehyde content of rats at 4 hr after a single i.p. injection of the carcinogen at a dose of 10 mg/kg. Neither the selenium-supplemented nor the selenium deficient animals exhibited any significant alteration in lipid peroxidation as a result of carcinogen administration. In con trast, the administration of carbon tetrachloride (i .5 mI/kg) resulted in a statistically significant increase in the hepatic malondialdehyde concentration of selenium-deficient animals and a less marked increase in selenium-supplemented rats. The results of these experiments indicate that the protective effect of dietary selenium against 2-acetylaminofluorene-in duced hepatocarcmnogenesis in rats is not mediated by an alteration in the binding of the carcinogen to liver DNA. Rather, the anticarcinogenic action of selenium appears to be related, at least in part, to its ability to protect hepatic DNA against indirect damage induced by the administration of 2-acetylami nofluorene. This protectiveeffect of selenium is readily over come by increasing the dose of the carcinogen. Moreover, under these conditions, dietary selenium has no apparent effect on the rate of DNA repair.