Activation of murine leukaemia virus under different physiological conditions

Abstract

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.

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

“…The transmission of these leukaemic lesions, consistently showing abundance of exclusive Cyt. A particles in successive passages, to syngeneic and allogeneic hosts by acellular extracts as well as high-centrifugal pellets have been reported earlier from our laboratory (Karande et al, 1975). In our previous paper (Joshi et al, 1979) we demonstrated the expression of MuMTV-related antigen, probably the mammary leukaemia (ML) antigen in these ovarian-hormone-induced leukaemias with anti-MTV serum by the immunodiffusion method.…”

“…The IE2 leukaemic line has been kept in serial transplantation in strain ICRC and DBA-MTI through cell-free extracts (Karande et al, 1975). Type A particles were isolated and purified from IE2 leukaemic line and mammary tumours of strains ICRC and C3H(Jax) according to the method of Tanaka (1977) which is an improved version of his original method reported in 1972 (Tanaka et al, 1972).…”

“…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). It was then thought that this was perhaps due to the rapid replication of latent mammary-tumour virus (MTV) in lymphoid cells under suitable conditions.…”

Potentiating Effect of Methyl Methane Sulfonate on Friend Virus Leukemogenesis in Vivo

“…Ball and McCarter (3) and Igel et al (4) subsequently demonstrated reproducible activation and production of leukemia virus after treatment with chemical carcinogens. These findings have been confirmed in a number of in vivo and in vitro studies suggesting that interaction with exogenous (5)(6)(7)(8)(9)(10)(11)(12) or endogenous (13)(14)(15)(16) viruses may play an important role in the production of some tumors by chemical carcinogens (also see 17 for review). More recently, Pottathil ef al.…”