The induction of
neoplastic cell transformation is closely associated with
DNA alterations which occur shortly after
carcinogen exposure. Sister chromatid exchange (SCE) formation is a sensitive
indicator of
carcinogen-
DNA interaction and correlates with the induction of morphological cell transformation. The persistence of lesions generating SCE produced by chemical and physical
carcinogens and its relevance to the induction of morphologic transformation was evaluated in coordinated experiments with cultured Syrian hamster fetal cells (HFC). Exponentially growing HFC were exposed for 1 h to
benzo[a]pyrene (BP),
methyl-methanesulfonate (MMS),
cis-platinum (II) diaminedichloride (cis Pt II),
N-methyl-N'-nitrosourea (MNU),
mitomycin C (MMC),
N-methyl-N'-nitro-N-nitrosoguanidine (
MNNG), N-acetoxy-2-fluorenyl-acetamide (AcAAF) or u.v. light irradiated. Cells were incubated for 24 h with
5-bromodeoxyuridine (BrdUrd) required for SCE visualization at 1, 24 and 48 h after
carcinogen exposure. The induction of morphological transformation was determined on the quantitative colony assay at 6 days after
carcinogen treatment. SCE analysis demonstrates that for a period of 48 h after
carcinogen exposure, during which time the cells undergo at least four replicative cycles, DNA damage generating SCE induced by all chemical
carcinogens either persisted or was partially removed, whereas u.v.-induced lesions were completely removed. An elevated SCE frequency persisted after two additional cell cycles
after treatment with BP, AcAAF or MMC without increased cell lethality as compared to other
carcinogens whose lesions were completely eliminated during the same period. Although a correlation between the persistence of SCE and the induction of transformation was not observed for all
carcinogens, this study illustrates that DNA damage generating SCE can persist over several replicative cycles, thus raising the possibility that lasting
DNA alterations are important for the induction of
neoplastic cell transformation.