Synergism between smoking and arsenic exposure in lung injury

Epidemiological evidence indicates that cigarette smoking and arsenic exposure act synergistically to increase the incidence of lung cancer. Experiments were designed to examine the possible mechanisms responsible for this syncrgism. Male Syrian golden hamsters were exposed via nose only for S days/week for 28 days to either air, cigarette smoke (5 cigarettes over a one hour period), arsenic (arsenic trioxide, 20μg/m³), or both arsenic and cigarette smoke. Combined exposure to arsenic and cigarette smoke led to significant decreases (20% of control values) in the total amount of glutathione. Values for smoke alone or arsenic alone exposures were at control levels. Reduction in total glutathione was due to loss of GSH, since GSSG levels were not significantly different between the groups. Loss of glutathione was correlated with a 5 fold increase in DNA oxidation in the smoke plus arsenic exposure group. Increases in DNA oxidation were not due to synergistic increases in lung inflammation since total cell counts were not significantly increased in the combined exposure group. These data indicate that combined exposure to cigarette smoke and arsenic can suppress glutathione levels in the lung. This may allow arsenic to inhibit DNA repair enzymes, thus increasing the levels of DNA oxidation.