1,2-Dimethylhydrazine carcinogenesis in neonatally androgenized CBA mice

Abstract

The aim of this study was to investigate the possible influence of exposure to steroid hormones early in life on the susceptibility of animals as adults to chemical carcinogens. CBA male and female mice received a single subcutaneous injection of 0.5 mg testosterone propionate (TP) in olive oil within 24 h after birth. At the age of 2 months, neonatally androgenized and control mice started receiving weekly subcutaneous injections of 1,2-dimethylhydrazine (DMH). By the end of the experiment, 90% of neonatally androgenized females treated with DMH developed uterine sarcoma against 9% in control females treated with DMH, this difference being attributed to the hyperoestrogenization of androgenized females. In neonatally androgenized males treated with DMH 79% developed pararenal sarcoma and 71% colon tumours versus 25 and 32% respectively of control males treated with DMH.

1,2-dimethylhydrazine carcinogenesis in C3HA and CBA female mice prenatally treated with diethylstilbestrol

“…However, taking this into account, the incidence between the group treated with DES and DMH, on the one hand, and the group treated with DMH alone on the other remains rather important. These results coincide, in principle, with those obtained in the experiments in which adult CBA females were treated with DMH and EP [9] and also with those in the androgenized mice treated with DMH [7]. In both of these studies, the effect of hyperestrogenization-exogenous or endogenous as in case of the neonatal androgenization-was much more pronounced (much higher uterine tumor incidence and much earlier appearance) than in the experiment presented here.…”

“…Changes in the incidence of these tumors in some groups were not confirmed in the others. No clear-cut effect on the colon tumors was found in the neonatally androgenized CBA female mice treated with DMH [7].…”

“…These mesenchymal lesions of the ovaries and of the uterus are strongly sex hormone dependent [5,6] and therefore seem to be a convenient model for studying the effect of perinatal hormone treatment. A previous study in CBA mice has shown that neonatal androgenization greatly altered the carcinogenesis induced by a subsequent DMH treatment [7].…”