The purpose of this study was to determine the carcinogenic effect in male rats of a single i.v. injection of
N-methyl-N-nitrosourea (MNU) after sequential treatment with
cyproterone acetate (for 21 days) and
testosterone propionate (for 3 days). This treatment has previously been shown to induce
carcinomas of the prostate and other male accessory sex glands. A wide spectrum of non-
melanoma skin
tumors was found in 38-48% of Wistar (Cpb:WU) rats given this sequential treatment, but only in 5% of rats that received only MNU.
Castration long and, particularly, early after MNU markedly reduced this skin
tumor response to
a 10-13% incidence. The skin tumorigenic efficacy of MNU was dependent on the time between the start of the
testosterone propionate treatment and
carcinogen administration: MNU injection after 48-50 or 60-63 h induced skin
tumors in 17-21% of Wistar rats, whereas injection after 72-74 h induced a 48% incidence. The Fischer F344 and Sprague-Dawley strains were not very sensitive to induction of skin
tumors by this approach. Thyroid follicular cell
tumors were also induced by MNU only after the hormonal pretreatment, and their induction was influenced by the time of MNU injection as well. The time of MNU injection and rat strain used did not significantly influence the induction of sebaceous-squamous
neoplasms of the ear-duct/Zymbal's glands or other
tumors. These data indicate that endogenous
androgens are critically involved in the later stages of rat skin
tumorigenesis and suggest that
androgen-induced cell proliferation influences the initiation stage of this process and, possibly, of thyroid
tumorigenesis.