Influence of hormones and chemical carcinogen on murine leukaemia

Leukaemogenesis induced with chemical carcinogens and hormones was studied in intact and ovariectomized mice of the ICRC strain which is susceptible to spontaneous development of both breast cancer and leukaemia and the Strong A strain susceptible only to breast cancer and not to leukaemia. In ovariectomized females oestradiol was administered at two dose levels (i) 1 μg oestradiol/day for 30 days, (ii) 10 μg oestradiol/day for 30 days. The effect of oestradiol (1 μg/day) and progesterone (1 mg/day) for 30 days was also studied. In one group, two pituitaries of the syngeneic male mice were implanted subcutaneously on the right inguinal pair of mammary glands. Enhancing effect of 20-MCA on leukaemogenesis was seen in intact strain ICRC mice and not in ovariectomized mice. However, administration of hormones, either oestradiol alone or in combination with progesterone, or by the way of pituitary grafts, to these carcinogen treated ovariectomized females increased the incidence of leukaemia with a shorter latent period. Although 20-MCA could induce leukaemogenesis in Strong A ovariectomized females, further treatment with hormones, either with pituitary graft or with oestradiol, failed to promote leukaemogenesis. The highest leukaemia incidence in strain A ovariectomized females was observed in the group treated with a balanced dose of oestradiol and progesterone. The present experimental findings in the ICRC and Strong A strains suggest specific differential responses of different strains of mice to the action of carcinogen and hormones for the induction of leukaemogenesis.