Methylated DNA adducts in the large intestine of ICR/Ha and C57BL/Ha mice given 1,2-dimethylhydrazine.
The site-specific incidence of 1,2-dimethylhydrazine (DMH)-induced neoplastic changes in intestinal segments of ICR/Ha mice correlates with the persistence of O6-methylguanine (O6MGua) after a single carcinogen injection. Six hours after the injection, the amount of O6MGua in four anatomic (proximal to distal) segments was 16.0, 20.8, 37.5, and 52.8 mumol/mol guanine, respectively. Correlation between the incidence of neoplasms and the amount of alkylation was also observed 14, 40, and 96 hours after DMH treatment. Similar levels of O6MGua were found in the corresponding colon segments of C57BL/Ha mice. After repeated treatment (5 wk) with unlabeled DMH, the amount of O6MGua still correlated with the incidence of neoplasms in ICR/Ha mice. However, in each strain the level of O6MGua was significantly lower in pretreated mice than in mice without DMH pretreatment. Furthermore, the amount of adducts in DNA isolated from different crypt depths showed that within a few hours of the DMH injection the amount of adducts was independent of DNA synthetic activity. Although ICR/Ha and C57BL/Ha mice have different susceptibility to DMH-induced colon cancer, this interstrain difference is not reflected in the amounts or persistence of the miscoding base O6MGua.
D019813:1,2-Dimethylhydrazine; D000818:Animals; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced*; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism*; D004127:Dimethylhydrazines / Q000633:toxicity*; D004198:Disease Susceptibility; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D007420:Intestine, Large / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008745:Methylation; D008763:Methylhydrazines / Q000633:toxicity*; D051379:Mice; D011230:Precancerous Conditions / Q000139:chemically induced*; D013045:Species Specificity; D013997:Time Factors
D002273:Carcinogens; D004127:Dimethylhydrazines; D008763:Methylhydrazines; D006147:Guanine; D004247:DNA; C008449:O-(6)-methylguanine; D019813:1,2-Dimethylhydrazine