DNA Repair Synthesis in Mammalian Cells exposed to a Series of Oncogenic and Non-Oncogenic Derivatives of 4-Nitroquinoline 1-Oxide

Abstract

IT has been repeatedly proposed that neoplastic cells arise from genetically heterogeneous populations. If so, carcinogens should induce genetically abnormal cells by increasing the frequency of mutations. The mutagenic capacity of carcinogens has been examined in Drosophila^1,2, Neurospora³, yeast⁴, transforming DNA⁵, and template activity of DNA⁶. Until recently, however, a study of chromatid aberrations and structural and numerical chromosome anomalies was the only way to examine the mutagenic effect of carcinogens on the tissues of complex organisms in which they induce neoplastic transformation^7,8. The disadvantage of this method lies in its restriction to numerical and structural chromosome alterations which represent only a part of the wide spectrum of all possible genetic changes elicited by a mutagen. In the work to be described here we have used unscheduled DNA synthesis as an indicator of DNA lesions^9–11. Derivatives of 4-nitroquinoline 1-oxide (4NQO) and related compounds were chosen because of their wide variance in oncogenic capacity^12–15. Cultured Syrian hamster cells of the first to third passage were used. These cells are susceptible to neoplastic transformation in vivo^12–21 and in vitro^22–23 after exposure to the carcinogens used. Moreover, they respond to 4NQO induced DNA lesions with a readily analysed DNA repair synthesis²⁴.