Increased sensitivity of xeroderma pigmentosum cells to some chemical carcinogens and mutagens

Abstract

The clone-forming capacity and level of DNA repair was examined on normal human cells and repair-deficient Xeroderma pigmentosum (XP) fibroblasts exposed to various chemical carcinogens and mutagens. The cultured fibroblasts were treated for 90 min with the carcinogenic and mutagenic 4-nitroquinoline 1-oxide (4NQO), 4-hydroxyaminoquinoline 1-oxide (4HAQO), 2-methyl-4-nitroquinoline 1-oxide (2-Me-4NQO), 3-methyl-4-nitropyridine 1-oxide 3-Me-4NPO) and the non-carcinogenic 6-nitroquinoline 1-oxide (6NQO). The response of the cells to the N-oxides was compared to that induced by the mutagen and carcinogen N-methyl- N′-nitro- N-nitrosoguanidine (MNNG) and UV-irradiation. The XP cells showed ( 1) a reduced level of DNA repair synthesis when exposed to various carcinogenic N-oxides, ( 2) no unscheduled DNA synthesis following 6NQO and ( 3) a normal degree of DNA repair synthesis after treatment with MNNG. When the clone-forming capacity was examined the XP cells exhibited ( 1) a higher increased sensitivity to the various carcinogenic N-oxides, ( 2) no reduction in the clone formation following 6NQO and ( 3) a sensitivity virtually comparable to that of normal cells after treatment with MNNG. The results suggest a link between extent of DNA damage, level of DNA repair and degree of sensitivity in human cells exposed to various chemical carcinogens and which induce DNA alterations that cannot be repaired by DNA repair synthesis.