Sister chromatid exchanges induced by mutagenic carcinogens in normal and xeroderma pigmentosum cells

Abstract

XERODERMA pigmentosum (XP) is a human disease characterised by sensitivity to sunlight¹, a high incidence of skin cancer¹ and a deficiency in DNA repair². Investigations of DNA damage and repair in XP cells exposed to chemical carcinogens^3–8 had led to the classification of these agents in two groups: those in which damage can be repaired by apparently normal levels of excision repair (for example, monofunctional alkylating agents) and those in which it cannot (for example, 4-nitroquinoline-1-oxide) (Table 1). In XP cells, normal excision of MMS⁹ or MNNG¹⁰ damage is correlated with normal levels of chromosome aberrations, and reduced excision repair of 4NQO damage is correlated with high levels of chromosome aberrations⁹, indicating that unrepaired damage is correlated with high levels of aberrations. It has recently been found that although sister chromatid exchanges (SCEs) differ from aberrations in many ways, they are far more sensitive indicators of chromosomal damage¹¹. We therefore considered that a comparison of excision repairability with the yields of SCEs induced by chemicals might be informative in elucidating mechanisms of SCE formation. The results indicate that, contrary to the results with aberrations, the frequency of induced SCEs is higher in XP cells than in normal cells whether or not XP cells can perform normal amounts of excision repair of the chemically-induced damage. The data indicate that the lesions and/or subsequent events that give rise to chromosome aberrations are different from those leading to sister chromatid exchange and that SCE formation in XP cells is the most sensitive mammalian system yet described for detecting possible genetic effects of chemicals.