Comparison of the effects of hydrogen peroxide and X-ray irradiation on toxicity, mutation, and DNA damage/repair in mammalian cells (V-79)

Abstract

Hydrogen peroxide is not detectably mutagenic at the hypoxanthine-guanine phosphoribosyl transferase locus (measured as 6-thioguanine resistance) in V-79 Chinese hamster lung cells, yet is cytotoxic with a D o dose of 240 μM. X-ray, by contrast, is both mutagenic and cytotoxic with a D o dose of 260 rad for cytotoxicity. The number of DNA single-strand breaks induced at equitoxic doses is much greater for hydrogen peroxide than it is for X-ray. Single-strand breaks are repaired with initial t 1 2 values of 5.0 min for X-ray and 6.8 min for hydrogen peroxide; after 12.5 min X-ray repair becomes biphasic, whereas H 2O 2 repair remains linear. Hydrogen peroxide does not induce either DNA-protein or DNA-DNA crosslinks, although X-ray has been previously shown to induce DNA-protein crosslinks. Hydroxyl radical scavengers reduce the number of DNA single-strand breaks induced by hydrogen peroxide and X-ray, which implies that hydroxyl radicals may mediate the formation of these breaks. Because hydroxyl radicals are produced by both agents, yet only X-ray is mutagenic, we conclude that hydroxyl radicals are not necessarily mutagenic in V-79 cells. The implications of these findings for the detection of carcinogens and mutagens is discussed.