Relationship of carcinogen-induced sister chromatid exchange and neoplastic cell transformation

Sister chromatid exchange (SCE) and morphological transformation induced by five chemical carcinogens, N-acetoxy-2-fluorenyl-acetamide (AcAAF), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methyl methanesulfonate (MMS), benzo[a]-pyrene (BP), and cisplatinum(II) diamine dichloride (PT) as well as by X-irradiation were quantified in parallel experiments with cultures of Syrian hamster embryo cells (HEC). Incubation of HEC with 5-bromodeoxyuridine (10(-5)M) for two rounds of replication (24 h) required for SCE visualization neither caused morphological transformation nor altered the transformation frequency induced by carcinogen alone. All chemical carcinogens, but not X-irradiation, produced a dose-dependent increase in SCE and transformation frequency, demonstrating the sensitivity of both assays to carcinogens. The ratios of induced SCE relative to transformation frequency, however, varied with the carcinogen. BP, MMNG, and AcAAF were similarly efficient in inducing SCE compared to transformation but were considerably less effective than MMS and PT. X-irradiation at doses of 200, 300, and 500 R did not cause transformation and induced a low frequency of SCE. On a molar basis, MMS and PT were the most effective in SCE induction relative to transformation, MNNG and AcAAF were less effective, and BP was the least effective carcinogen. The positive linear correlation between chemical carcinogen-induced SCE and transformation suggests a relationship between the two cellular responses.