DNA damage and its repair in human normal or xeroderma pigmentosum fibroblasts treated with 4-nitroquinoline 1-oxide or its 3-methyl derivative

Abstract

Normal human or excision deficient xeroderma pigmen-tosum (XP) fibroblasts were exposed to either the potent carcinogen 4-nitroquinoline 1-oxide (4NQO) or the weaker acting 3 methyl derivative of this compound. The inhibition of cell growth, DNA damage and DNA repair were then monitored in these cells. The data indicate that the modification of 4NQO by methylation actually changes the type and amount of DNA damage induced by this carcinogen. More specifically, the methylation of 4NQO at the three position prevented the formation of 4NQO induced DNA adducts manifesting themselves as alkaline stable lesions whose repair was cytosine arabinoside inhibitable in normal cells, but defective in excision deficient XP cells. Alkaline labile lesions induced by 4NQO which are repairable in the above XP cells were still induced by the 3 methyl derivative but a lower frequency on an equimolar basis.