title: Comparative study of DNA adduct formation in mice following inhalation of smoke from cigarettes that burn or primarily heat tobacco.
abstract: 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. Micronuclei formation in bone marrow and peripheral blood polychromatic erythrocytes (PCE) of animals exposed to either the TOB-HT or 1R4F cigarette was not significantly different compared with control animals exposed nose-only to filtered and humidified air (sham controls). DNA adduct measurement by the 32P-post-labeling method indicated an exposure-dependent increase in lung adducts of animals exposed to 1R4F cigarette smoke at all three concentrations with the mid and high exposure groups exhibiting statistically significant increases (P < 0.05) in adduct formation compared to sham-exposed animals. The concentration of DNA adducts in the lungs of animals exposed to the TOB-HT cigarette was not significantly increased (P < 0.05) at any concentration compared to sham-exposed controls. A statistically significant (P < 0.05) concentration-dependent formation of DNA adducts was also observed in the heart tissues of animals exposed to smoke from the 1R4F cigarette at all three concentrations, but no significant increase in adduct formation was observed in heart DNA of the animals exposed to the TOB-HT cigarette (P < 0.05). Under the conditions of this experiment, the mainstream smoke from the TOB-HT cigarette was demonstrated to be less genotoxic in mice than mainstream smoke from the 1R4F cigarette, which is representative of cigarettes in the current U.S. market.
authors.affiliation: Environmental and Molecular Toxicology Division, RJ Reynolds Tobacco Company, Winston-Salem, NC 27102, USA.
authors.forename: B G
authors.initials: BG
authors.lastname: Brown
authors.forename: C K
authors.initials: CK
authors.lastname: Lee
authors.forename: B R
authors.initials: BR
authors.lastname: Bombick
authors.forename: P H
authors.initials: PH
authors.lastname: Ayres
authors.forename: A T
authors.initials: AT
authors.lastname: Mosberg
authors.forename: D J
authors.initials: DJ
authors.lastname: Doolittle
mesh_terms: D000818:Animals; D018736:DNA Adducts; D006321:Heart / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D009206:Myocardium / Q000378:metabolism; D010947:Plants, Toxic; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
chemical_list: D018736:DNA Adducts; D009153:Mutagens; D012906:Smoke