The influence of antioxidants on cigarette smoke-induced DNA single-strandbreaks in mouse organs: A preliminary study with the alkaline single cell gel electrophoresis assay

According to published information, the lung is the only clear target organ for tumors when mice are exposed to cigarette smoke. Liver, skin, and uppe r digestive tract are target organs when orally or dermally exposed to ciga rette smoke condensate, but not kidney, brain, or bone marrow. We tested th e genotoxicity of cigarette smoke in the known target organ (lung), possibl e target organs (stomach and liver), and non-target organs (kidney, brain, and bone marrow) of the mouse using the alkaline single-cell gel electropho resis (SCG, or comet) assay, as modified by us. We also tested the effect o f free radical scavengers on the genotoxicity of the smoke. Male ICR mice w ere exposed to cigarette smoke. DNA single-strand breaks (SSB) were measure d by the SCG assay 15, 30, 60, 120, and 240 min after the exposure. Fifteen min after the animals were exposed for 1 min to a 6-fold dilution of smoke , SSB appeared in the lungs, stomach, and liver; the damage in the longs an d liver returned to almost control levels by 60 min, and that of the stomac h by 120 min. Kidney, brain, and bone marrow DNA were not damaged. Exposure to more dilute smoke (12- or 24-fold dilution) did not cause DNA damage. S ingle oral pretreatment (100 mg/kg) of either ascorbic acid (VC) or cu-toco pherol acetate (VE) 1 h before smoke inhalation prevented SSB in the stomac h and liver, while VE but not VC significantly reduced SSB in the lung, Fiv e consecutive days of either VC or VE (100 mg/kg/day) pretreatment complete ly prevented SSB in the lung, stomach, and liver. Thus, the SCG assay detec ted DNA SSB, induced by cigarette smoke, in the known target organ, two pos sible target organs, and none of the non-target organs. Antioxidants could prevent those effects, suggesting that free radicals may have been a source of the damage. Our results suggest the importance of the SCG assay as a to ol in the study of genotoxicity and carcinogenicity.