Southern synergy.

Aflatoxin B, (AFB,) induced rat liver cancer is a well studied system of hepatocarcinogenesis. AFBI has also been used to transform cultured rat liver derived cells in vitro. Cells in culture often have a reduced capacity to metabolise the AFB, to its active metabolite, and often prolonged periods of exposure to the toxin have to be employed, with a long latency in the appearance of transformed cells in culture. We report here the transformation of a rat liver derived cell line by acute treatment with AFB. An extrinsic metabolising system of quail microsomes, which convert AFB1 to its epoxide form with high efficiency, was used to activate the AFB,. A dose dependent cytotoxicity was obtained and neoplastic transformation was seen in the higher doses used. The enzyme GGT which has strong association with liver cell transformation both in vivo and in vitro was also elevated in the treated cells. Aflatoxins are fungal toxins which have been implicated in human liver cancer. There is an extensive array of rat liver carcinogenesis systems to elucidate the steps involved in the development of neoplasia (Newberne et al., 1973, Kalengayi et al., 1975). Transformation of liver cells by aflatoxin in tissue culture is complicated by the requirement for metabolic activation of the toxin (Campbell & Hayes, 1976). Primary cultures of hepatocytes lose their ability to metabolise aflatoxin to its active form by a cytochrome P-450 mediated pathway within 48 h in culture (Guzelian et al., 1977) and so far there have been no reports of the transformation of non-dividing hepatocyte cultures in vitro by exposure to aflatoxin. Continuously dividing cell lines are more susceptible to malignant transformation than primary cultures, and have been used to study the effects of a variety of carcinogens. Non-transformed, continuously dividing cell lines arise spontaneously from primary cultures of rat liver cells. They are non-tumorigenic in syngeneic hosts and in athymic nude mice, and lack the biochemical characteristics of mature rat hepatocytes. It is hypothesised that these cell lines arise from a population of precursor cells in the liver (Grisham, 1980). BL8 is an undifferentiated untransformed cell line arising spontaneously from cells isolated from the liver of an adult male Fischer rat (Manson et al., 1981). It has the ultra-structural features of an epithelial cell. After transformation by activated ras oncogenes it shows the induction of gamma glutamyl transferase, a marker of liver cell transformation and is tumorigenic in …