[Is hypomethylation of cellular DNA a step required in the initiation process of chemical carcinogenesis?].
There seems to be a current view that the inhibition of DNA methylation may be a mechanism of initiation of carcinogenesis or one of the steps required in the carcinogenic process. However, because of the deficiencies in research works on cellular level, there is a long way to make such a general relationship between carcinogen and the inhibition of cellular DNA methylation. In this paper the effects of some chemical carcinogens on methylation of newly replicated DNA in human FL cells was analyzed by comparing the weight average length (Lw) of the DNA digests after complete digestion by restriction endonuclease Hpa II. It was observed that two non-genotoxic carcinogens (5-azacytidine and L-ethionine) and two genotoxic carcinogens (MNNG and aflatoxin B1) used in this study all caused obvious cytotoxicity on FL cells at the test concentration. Five days after the termination of 5-azacytidine treatment (2 x 10(-6) M, 24 hours), Lw (kb) of the Hpa II digests of cellular DNA was smaller than that of control (8.0 +/- 0.1 vs 10.9 +/- 1.0, P less than 0.01), the Lw change rate was -27%. When DNA was analyzed from FL cells after 9 days continuous treatment of L-ethionine (2 x 10 M), the digestibility of Hpa II was also increased as compared with that of the control, the Lw values (kb) showed a decrease of about 8% (9.8 +/- 0.3 vs 10.6 +/- 0.3, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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D016604:Aflatoxin B1; D000348:Aflatoxins / Q000494:pharmacology; D000650:Amnion / Q000166:cytology*; D001374:Azacitidine / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004847:Epithelial Cells; D005001:Ethionine / Q000494:pharmacology; D006801:Humans; D008745:Methylation; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology
D000348:Aflatoxins; D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; D004247:DNA; D016604:Aflatoxin B1; D001374:Azacitidine; D005001:Ethionine