Criterion Development for the Application of BALB/c-3T3 Cells to Routine Testing for Chemical Carcinogenic Potential

Abstract

Short-term in vitro cell transformation assays have emerged as potentially powerful tools for the evaluation of pure chemicals and complex mixtures for their carcinogenic potential. Among the more widely applied of these systems are the BALB/c-3T3 (Kakunaga, 1973), C3H/10T1/2 (Reznikoff et al., 1973), and Syrian hamster embryo (Berwald and Sachs, 1965; DiPaolo et al., 1971) cell transformation assays, although a variety of other related systems have been described (Casto et al., 1974; Evans and DiPaolo, 1975; Freeman et al., 1970; Kakunaga, 1978; Milo and DiPaolo, 1978; Traul et al., 1979; and see Heidelberger, 1981 for a recent review). Each of these systems measures chemical induction of alterations in cell colony or focus morphology and in each case, these alterations have been shown to be correlated with the acquisition of cellular malignant properties (DiPaolo et al., 1971; Kakunaga, 1978; Reznikoff et al., 1973). Thus, the strength of in vitro cell transformation assays, in the context of chemical carcinogen screening, lies in their apparent phenomenological relation to the process of carcinogenesis per se. At the same time, these assay systems exhibit significant technical as well as theoretical difficulties in their conduct and evaluation.