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.
Bibliographical noteFunding Information:
We wish to thank Dr A.Mode for kindly providing the sex-specific CYPIICU and CYPIIC12 clones. This work was supported by the NIH (CA57925-01), the Swedish Cancer Society, the Research Funds of the Royal Swedish Academy of Sciences and the Ake Wiberg Foundation.