176 INDUCTION OF MURINE C - TYPE VIRUSES Cells

There is now considerable evidence that spontaneous leukemias in mice are caused by C-type RNA viruses. These viruses appear to be capable of existing in the animal in an unexpressed form for many generations. In inbred mouse strains such as C58 and AKR, in which virus can be detected early in life, leukemia develops at high frequency in young animals (1, 2). In other strains such as BALB/c or C57BL/6, virus is first detectable in older mice; in these strains leukemia appears at a much lower frequency in late life (2, 3) or after exposure to X-irradiation or chemical carcinogens (3, 4). Some strains such as NIH Swiss have a very low incidence of leukemia; and C-type viruses have yet to be isolated. In tissue culture, evidence that an endogenous C-type viral genome can exist in an unexpressed state in mouse cells was presented in studies of BALB/c and random-bred Swiss mouse embryo cells (5). Certain cell lines derived from virus-negative primary embryos were shown to produce virus spontaneously after many generations in culture. More recent studies have shown that activation of virus production can be greatly enhanced by treatment of mouse cells with certain chemical andphysical agents (6, 7) ; these studies demonstrate that C-type viruses are present in an unexpressed form in all AKR (6, 7) and BALB/c cells (8, 9).