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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.

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Summary.-The leukaemic lesions in intact and ovariectomized mice of strain ICRC, induced with 20-methylcholanthrene (20-MCA) in combination with or without hormones were investigated for the presence of mouse leukaemia virus (MuLV) by (i) bioassays and (ii) electron microscopy. The different experimental groups treated with 20-MCA were (i) intact females, (ii) ovariectomized females, (iii) ovariectomized females with pituitary graft, (iv) ovariectomized females with 10 jg oestradiol/day for 30 days and (v) ovariectomized females with 1 ,g oestradiol together with 1 mg progesterone/day for 30 days. It was possible to trahismit nearly all these experimentally induced leukaemias to syngeneic mice thtough acellular extracts, compared with very poor transmissibility of spontaneous leukaemias in the ICRC strain, indicating functional activation of viral agents on combined treatment with carcinogen and hormones. Potency of the acellular leukaemic extract from the mice of group (ii) without the ovarian hormones was much weaker than that from mice of the other experimental groups. The leukaemogenic activity of MuLV was enhanced on serial transmission in syngeneic hosts. Leukaemic lesions of ovariectomized mice treated with 20-MCA and oestradiol were also transmissible to the sucklings of allogeneic mice of strain C3H-MTV, C57-BL and Dba-MTV. The cell-free supernatant medium of the cultures of these leukaemic lesions induced leukaemias on back inoculation into syngeneic mice. Electron microscopic studies of lesions induced with carcinogen and oestradiol consistently showed abundant intracytoplasmic type A particles. Numerous intracytoplasmic type A particles as well as some type B particles were found in the leukaemic tissues of ovariectomized females treated with MCA and oestradiol combined with progesterone. Type C particles, characteristic of MuLV were seen in the leukaemic tissues of all other experimental groups. These findings indicate a significant influence of the physiological condition of the host, particularly the hormonal make up, on expression and activity of specific viral agents.

The response to gonadectomy was shown to vary in two cancer-susceptible strains of mice, C3H/Jax and ICRC. In the strain ICRC, unlike strain C3H, adrenocortical response to gonadectomy was completely absent. The cytology of the pituitaries was studied in different age groups of these strains and the gonadotrophin content of the pituitaries after ovariectomy was determined.A consistent increase in the number and size of the gonadotrophs accompanied by a rise in the storage of pituitary gonadotrophins was demonstrated after ovariectomy. These changes were much more pronounced and occurred earlier in strain C3H than in strain ICRC. The responses of strain ICRC closely resembled those of the cancer-resistant strain C57. It is suggested that the pituitary gonadotrophic response to gonadectomy is inadequate in strain ICRC which leads to the lack of responses from adrenal cortex and thus to the oontrol of breast cancer development.