Influence of gonadal hormones and age on 1,2-dimethylhydrazine-induced colon carcinogenesis.
BD-II and BD-IX male and female rats received weekly subcutaneous (s.c.) injections of 15 mg/kg 1,2-dimethylhydrazine dihydrochloride (DMH) beginning at either 35, 120 or 210 days of age and continuing for 20 weeks. Control animals received only the DMH vehicle. Additional BD-II and BD-IX male and female rats of the three age groups were gonadectomized at 21, 106 and 196 days. Beginning 14 days after gonadectomy, the rats received 15 mg/kg of DMH by s.c. injection once a week for 20 weeks. Animals were sacrificed 35 weeks after the initial DMH injection. Control rats of the appropriate age and sex did not develop colon tumors. BD-IX rats are apparently more sensitive to DMH than BD-II rats. The incidence of DMH-induced cancer is less in females than in males in both the BD-II and BD-IX animals. Gonadectomy does not affect cancer incidence in either BD-II males or females nor in the BD-IX females but reduced the incidence in BD-IX males exposed initially at either 120 or 210 days. Administration of androgen to castrate BD-IX males (120-day-old group) increases the incidence of colon cancer to that approaching the intact animal but has little effect in the BD-II castrate male. These data suggest a genetically influenced susceptibility to DMH-induced colon carcinogenesis between BD-II and BD-IX rats. Furthermore, a sex difference is evident in both BD lines but age appears to be a factor only in older BD-IX females. Apparently, androgens influence DMH-induced tumorigenesis in BD-IX males only if the initial exposure of DMH occurs after sexual maturity.
D000230:Adenocarcinoma / Q000139:chemically induced*; D000375:Aging; D000818:Animals; D002369:Castration; D003110:Colonic Neoplasms / Q000139:chemically induced*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004127:Dimethylhydrazines / Q000633:toxicity*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D008297:Male; D008763:Methylhydrazines / Q000633:toxicity*; D051381:Rats; D012737:Sex Factors
D004127:Dimethylhydrazines; D012739:Gonadal Steroid Hormones; D008763:Methylhydrazines; D013196:Dihydrotestosterone