COMPARATIVE-STUDY OF DNA ADDUCT FORMATION IN MICE FOLLOWING INHALATION OF SMOKE FROM CIGARETTES THAT BURN OR PRIMARILY HEAT TOBACCO

The genotoxic potential of mainstream smoke from a test cigarette (TOB -HT) that primarily heats tobacco and a representative tobacco-burning cigarette (Kentucky reference 1R4F) was compared in male B6C3/F1 mice after nose-only inhalation exposure. Mice were exposed 1 hr per day, 5 days/week for a 4 week period to mainstream smoke at concentrations of 0, 0.16, 0.32, and 0.64 mg total particulate matter/liter of air. M icronuclei formation in bone marrow and peripheral blood polychromatic erythrocytes (PCE) of animals exposed to either the TOB-HT or 1R4F ci garette was not significantly different compared with control animals exposed nose-only to filtered and humidified air (sham controls). DNA adduct measurement by the P-32-post-labeling method indicated an expos ure-dependent increase in lung adducts of animals exposed to 1R4F ciga rette smoke at all three concentrations with the mid and high exposure groups exhibiting statistically significant increases (P < 0.05) in a dduct formation compared to sham-exposed animals. The concentration of DNA adducts in the lungs of animals exposed to the TOB-HT cigarette w as not significantly increased (P < 0.05) at any concentration compare d to sham-exposed controls. A statistically significant (P < 0.05) con centration-dependent formation of DNA adducts was also observed in the heart tissues of animals exposed to smoke From the 1R4F cigarette at ail three concentrations, but no significant increase in adduct format ion was observed in heart DNA of the animals exposed to the TOB-HT cig arette (P < 0.05). Under the conditions of this experiment, the mainst ream smoke from the TOB-HT cigarette was demonstrated to be less genot oxic in mice than mainstream smoke from the 1R4F cigarette, which is r epresentative of cigarettes in the current U.S. market. (C) 1997 Wiley -Liss, Inc.