Comparison of 7-medG formation in white blood cells, liver and target organs in rats treated with methylating carcinogens.
The relationship between 7-methylguanine (7-meG) formation in white blood cells (WBC) and internal organs after treatment with methylating carcinogens has been studied in rats, in order to assess the possible use of WBC as a surrogate for target organs in epidemiological studies. Animals were treated with a single intraperitoneal injection of DMN, DMH or NMBA or with a subcutaneous injection of NNK, at different dose levels, and killed 16 h after treatment. 7-meG, following thermal hydrolysis and immunopurification, was analysed by HPLC with electrochemical detection. Administration of methylating carcinogens resulted in the dose-dependent formation of 7-meG in WBC DNA; the adduct level, however, was markedly lower than in internal organs. The ratio between 7-meG formation in target organ and WBC was a function of the carcinogen administered, varying from 3.6 with NNK to 200 with NMBA. On the other hand, the ratio between 7-meG in the liver and WBC was of the same order of magnitude for each carcinogen, ranging from 35 to 100. These results show that the presence of 7-meG in WBC DNA is indicative of adduct formation in internal organs, particularly in the liver, and suggest that active methylating species may be formed in the liver and then transferred to the WBC where they can methylate DNA.
International Agency for Research on Cancer, Lyon, France.
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Bianchini
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D019813:1,2-Dimethylhydrazine; D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004247:DNA / Q000378:metabolism*; D004127:Dimethylhydrazines / Q000633:toxicity; D004128:Dimethylnitrosamine / Q000633:toxicity; D006147:Guanine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D007962:Leukocytes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008745:Methylation; D009602:Nitrosamines / Q000633:toxicity; D051381:Rats
D000477:Alkylating Agents; D002273:Carcinogens; D004127:Dimethylhydrazines; D009602:Nitrosamines; D006147:Guanine; C008450:7-methylguanine; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D004247:DNA; D019813:1,2-Dimethylhydrazine; D004128:Dimethylnitrosamine