Influence of Hormones and Chemical Carcinogen on Murine Leukaemia

Abstract

Summary.-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)]l Hg oestradiol/day for 30 days, (ii) 10 ,ug oestradiol/day for 30 days. The effect of oestradiol (1 ,tg/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.

Activation of murine leukaemia virus under different physiological conditions

“…The electron microscopic studies revealed paucity of type C virus particles, characteristic of murine leukaemia, in the spontaneous leukaemic tissues (Hiraki, Ranadive and Dmochowski, 1974). Studies on the experimental induction of leukaemia in castrates of this strain have confirmed the importance of hormones in the acceleration of leukaemogenesis (Karande and Ranadive, 1973 in olive oil, once a week by stomach tube for 8 wN-eeks. The carcinogen treated ovariectomized females were also given a daily dose of oestradiol alone and a dose of oestradiol with progesterone for a period of 30 days.…”

“…About 76% intact females treated with carcinogen, developed mammary cancer as well as leukaemia (Karande and Ranadive, 1973).…”

“…The role of hormones in accelerating leukaemogenesis in strain ICRC has been studied previously (Karande and Ranadive, 1973). Treatment with chemical carcinogens accelerated the process of leukaemogenesis in castrated ICRC mice, particularly when the carcinogen was administered together with the hormones.…”

“…In another group of ovariectomized mice, 2 pituitaries from isologous male mice wNere grafted subcutaneously onto the right inguinal pair of mammary glands. The detailed experimental procedure has been reported before (Karande and Ranadive, 1973). Extracts of leukaemic lesions wAere prepared for viral studies from the following groups: Group I (intact virgin mice treated with 20-MCA (Extract I)); Group II (ovariectomized mice treated with 20-MCA (Extract II); Group II (ovariectomized mice with 2 pituitary grafts and treated with 20-MCA (Extract III)); Group IV (ovariectomized mice treated with 20-MCA and 10 ,tg oestradiol/day for 30 days (Extract IV)); Group V (ovariectomized mice treated with 20-MCA and 1 ,ug oestradiol X-1 mg progesterone/day for 30 days (Extract V)).…”

Intracytoplasmic type A particles from mammary tumours and leukaemias of strain ICRC mice

“…STUDIES on the expression and activation of leukaemia virus after the administration of ovarian and pituitary hormones with 20-methylcholanthrene (MCA) in strain ICRC, have been reported from our laboratory (Karande & Ranadive, 1973). The leukaemias induced with 20-MCA plus oestradiol consistently showed abundance of intracytoplasmic type A particles in the leukaemic tissues when studied under the electron microscope (Hiraki et al, 1974;Karande et al, 1975).…”