Role of hormone imbalance in transplacental carcinogenesis induced in Syrian golden hamsters by sex hormones.
Data are presented from studies on Syrian golden hamsters with the ENU precursors, EU, and NaNO2, given transplacentally and in adulthood, and with transplacentally administered DES. Hormone modification by gonadectomy of offspring prenatally exposed to ENU caused a significantly greater incidence and multiplicity of PNS neoplasms and other tumor types in orchidectomized males, compared with intact males, and in ovariectomized and intact females. That PNS tumors in gonadectomized males appeared within a significantly shorter latency period indicated that endogenously generated androgens inhibited neoplastic development. The endocrine imbalance also induced a higher incidence of neoplasia in other tissues and organs, e.g., skin melanomas, thyroid and adrenal cortex tumors, and notably gliomas in the CNS of ovariectomized female siblings. Exposure to single doses of ENU on days 12, 13, 14, and/or 15 caused PNS tumors predominantly in females and with an increased frequency in progeny treated during the final days of gestation. The spectrum of neoplasms was greater and their incidence significant in ENU-treated adult hamsters; the tumor types different from those of transplacentally treated animals (i.e., vascular, vaginal, and ovarian tumors and fore-stomach papillomas were seen). Determining factors in carcinogenesis at the time of carcinogen treatment possibly included stage of ontogenic development, degree of cell differentiation, hormone state of host, age, total dose, and duration of treatment. DES results indicated that the haster may be a useful model for reproducing lesions similar to those observed in children of mothers treated with this drug during pregnancy.
D000818:Animals; D002369:Castration; D006224:Cricetinae; D004054:Diethylstilbestrol / Q000008:administration & dosage*; D005038:Ethylnitrosourea / Q000008:administration & dosage*; D005260:Female; D005833:Genital Neoplasms, Female / Q000209:etiology; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D008297:Male; D008431:Maternal-Fetal Exchange; D008647:Mesocricetus; D009374:Neoplasms, Experimental / Q000209:etiology* / Q000473:pathology; D009607:Nitrosourea Compounds / Q000008:administration & dosage*; D010053:Ovary / Q000502:physiology; D010524:Peripheral Nervous System Neoplasms / Q000209:etiology; D011247:Pregnancy; D013736:Testicular Neoplasms / Q000209:etiology; D013737:Testis / Q000502:physiology
D012739:Gonadal Steroid Hormones; D009607:Nitrosourea Compounds; D004054:Diethylstilbestrol; D005038:Ethylnitrosourea