Sister chromatid exchange as an indicator of mutagenesis

Abstract

SISTER chromatid exchange (SCE), that is, the reciprocal interchange of DNA between chromatids, is easily visualised in metaphase chromosomes^1,2 and has been applied to study chromosome structure^3,4, chromosome damage⁵, and instability and DNA repair deficiency syndromes^6–9. Since SCEs can be induced by subtoxic doses of carcinogens and mutagens^5,10–13, their analysis offers the possibility of a rapid, sensitive and quantitative assay for genetic damage. We have begun to examine the relation between SCEs and mutations in Chinese hamster ovary (CHO) cells by quantifying the induction of SCEs in parallel with the induction of mutations producing 8-azaguanine resistance, that is, mutations predominately at the hypoxanthine phosphoribosyltransferase, hprt, locus. Since the conversion of a chemically induced DNA lesion to a SCE or mutation may depend on the nature of that lesion, we tested four chemicals that differ in their interaction with DNA—ethyl methanesulphonate (EMS; O⁶: N⁷ guanyl alkylation ratio¹⁴ of 0.03), N-ethyl-N-nitrosourea (ENU; O⁶: N⁷ guanyl alkylation ratio¹⁵ of about 0.35), the crosslinking agent mitomycin C (MMC)¹⁶ and the intercalator proflavine sulphate (PRO)¹⁷. Our results indicate a linear relation between induced SCEs and mutations. The relative efficiency, however, is different for each chemical.