Sex differences at the initiation stage of rat liver carcinogenesis-influence of growth hormone

Male and female rats were initiated with a single dose of 3′-methyl-4-dimethylaminoazobenzene (3′MeDAB), N-hydroxy-2-acetylaminofluorene (N-OH-AAF) or aflatoxin B₁ (AFB₁) and promoted with 2-acetylaminofluorene plus partial hepatectomy (2-AAF/PH). One group of male rats in each experiment received continuous infusion of pituitary growth hormone (GH) for one week prior to initiation to feminize the secretory pattern of GH and hepatic functions. A significantly larger number of foci in male than in female rats was observed after N-OH-AAF and AFB₁ initiation. Continuous GH treatment of male rats decreased the number of N-OH-AAF-initiated foci to the level in females, while no effect of GH was observed on AFB₁ initiation. Initiation with 3′MeDAB showed no sex differences in number of foci. In conclusion, the present study demonstrates that sex differences occur at the initiation stage and that the secretory pattern of GH is responsible for the dimorphism in initiation with N-OH-AAF, but not with AFB₁.