Ninety-Day Inhalation Study in Rats, Using Aged and Diluted Sidestream Smoke from a Reference Cigarette: DNA Adducts and Alveolar Macrophage Cytogenetics

• Published in: Fundamental and applied toxicology Vol. 20; no. 4; pp. 393 - 401
• Main Authors: Lee, Chin K., Brown, Buddy G., Reed, Elizabeth A., Coggins, Christopher R.E., Doolittle, David J., Hayes, A.Wallace
• Format: Journal Article
• Language: English
• Published: Boston, MA Elsevier Science (USA) 01.05.1993; San Diego, CA Academic Press; New York, NY
• Subjects: Administration, Inhalation; Animals; Benzo(a)pyrene - metabolism; Biological and medical sciences; Carboxyhemoglobin - metabolism; Chromosome Aberrations; Cotinine - blood; DNA - drug effects; DNA - metabolism; Genetic Markers; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - ultrastructure; Male; Medical sciences; Nicotine - blood; Phosphorus Radioisotopes; Rats; Rats, Sprague-Dawley; Tobacco Smoke Pollution - adverse effects; Tobacco, tobacco smoking; Toxicology; Chromosomal aberration; Heart; Subchronic; Rat; Toxicity; Liver; Lung; Ageing; Rodentia; Inhalation; Suspended particle; Vertebrata; Tobacco; Mammalia; Urinary bladder; Animal; DNA; Cytogenetics; Passive smoking; Sidestream smoke; Molecular adduct; Macrophage
• ISSN: 0272-0590; 1095-6832
• DOI: 10.1006/faat.1993.1051

Ninety-Day Inhalation Study in Rats, Using Aged and Diluted Sidestream Smoke from a Reference Cigarette: DNA Adducts and Alveolar Macrophage Cytogenetics, Lee, C. K., Brown, B. G., Reed, E. A., Coggins, C. R. E., Doolittle, D. J., and Haves, A. W. (1993). Fundam. Appl. Toxicol. 20, 393-401. To study the genotoxic effects of subchronic exposure to environmental tobacco smoke, Sprague-Dawley rats were exposed to 0, 0.1, 1.0, and 10 mg total particulate matter (TPM)/m3 of aged and diluted sidestream smoke (ADSS) from 1R4F reference cigarettes 6 hr per day, 5 days a week for 13 weeks. DNA from lung, heart, larynx, bladder, and liver was tested for adduct formation by the 32P-postlabeling assay after 28 (except bladder) and 90 days of exposure and 90 days after cessation of exposure. In addition, alveolar macrophages from animals exposed for 28 or 90 days were examined for chromosomal aberrations. Exposure-related DNA adducts were not observed in any tissue in any of the animals exposed to 0.1 or 1.0 mg TPM/m3. However, increased levels of DNA adducts with diagonal radioactive zones were observed in lung, heart, and larynx DNA of animals exposed to the highest concentration of ADSS (10 mg TPM/m3). Adduct analyses with varying amounts of DNA from lungs of mid- and high-exposure animals clearly indicate that the dose-response for DNA adduct formation is nonlinear. The adduct levels were highest after 90 days of exposure and were significantly reduced in all target tissues 90 days after cessation of exposure. Chromosomal aberrations in alveolar macrophages were not elevated in any group after 28 or 90 days of exposure. These results indicate a no-observed-effect-level (NOEL) of at least 1.0 mg/m3 for DNA adduct formation in lung, heart, and larynx, and a NOEL of at least 10 mg/m3 for the induction of chromosome aberrations in alveolar macrophages, under the conditions of this study.