SMOKELESS TOBACCO INDUCED INCREASES IN HEPATIC LIPID-PEROXIDATION, DNA-DAMAGE AND EXCRETION OF URINARY LIPID METABOLITES

The possible role of reactive oxygen species in the toxicity of smokel ess tobacco (ST) was explored. The effects of an aqueous smokeless tob acco extract (SIE) at doses of 125, 250 and 500 mg STE/kg in rats on t he induction of hepatic mitochondrial and microsomal lipid peroxidatio n and the incidence of hepatic nuclear DNA damage 24 hours post treatm ent were examined. Dose-dependent increases of 1.8, 2.3 and 4.4-fold i n mitochondrial and 1.5, 2.1 and 3.6-fold in microsomal lipid peroxida tion occurred at 125, 250 and 500 mg STE/kg, respectively, relative to control values. At these same three doses of STE, 1.3, 1.4 and 2.7-fo ld increases in hepatic DNA single-strand breaks occurred relative to control values. STE administration also resulted in significant increa ses in excretion of urinary metabolites. Urinary excretion of the four lipid metabolites malondialdehyde (MDA), formaldehyde (FA), acetaldeh yde (ACT) and acetone (ACON) was monitored by HPLC for 72 hours after treatment of rats with 125 and 250 mg STE/kg. Increases occurred in th e excretion of the four lipid metabolites at every dose and time point with maximum increases in the excretion of all lipid metabolites bein g observed between 12 and 24 hours post treatment. The results suggest the involvement of an oxidative stress in the toxicity of STE.