Inhaled cigarette smoke induces the formation of DNA adducts in lungs of rats

Journal Article · Thu Jun 01 04:00:00 EDT 1989 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(89)90121-X· OSTI ID:5764176

Bond, J A; Chen, B T; Griffith, W C; Mauderly, J L

Cigarette smoking causes a variety of adverse human health effects, including lung cancer. The molecular events associated with smoke-induced carcinogenesis are thought to be related in part to the genotoxic activities of the chemicals associated with smoke. The purpose of this investigation was to determine the molecular dosimetry of compounds in cigarette smoke in lungs of rats exposed by inhalation. These studies investigated the effects of exposure mode, sex, and time (adduct persistence) on the level of DNA adducts. Male and female F344/N rats were exposed 6 hr/day, 5 days/week for 22 days to cigarette smoke by nose-only intermittent (NOI), nose-only continuous (NOC), or whole-body continuous (WBC) exposures. Separate groups of rats were sham-exposed nose-only (NOS) or whole-body (WBS) to filtered air. All smoke exposure modes yielded daily smoke exposure concentration X time products of 600 mg particulate.hr/m3 for the first week and 1200 mg particulate.hour/m3 thereafter. Groups of rats were killed at 18 hr and 3 weeks after the 22-day exposure period and DNA adducts in lung tissues were quantified by the /sup 32/P-postlabeling method. There were significant (p less than 0.05) increases in levels of clearly resolved lung DNA adducts in male and female rats exposed to smoke compared to sham-exposed rats. There were no significant effects of exposure mode or sex on lung DNA adducts. Mean levels (+/- SE) of clearly resolved lung DNA adducts for both sexes combined in NOI, NOC, WBC, NOS, and WBS groups were 50 +/- 4, 52 +/- 6, 52 +/- 7, 21 +/- 6, and 22 +/- 4 adducts per 10(9) bases, respectively. Levels of clearly resolved DNA adducts were significantly less in lungs of rats killed 3 weeks after exposure and had declined to near control levels, suggesting that smoke-induced adducts are repaired by lung DNA repair enzymes.

• Research Organization: Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM (USA)
• OSTI ID: 5764176
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 99:1; ISSN TXAPA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
AEROSOLS
ANIMALS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BIOSYNTHESIS
BODY
COLLOIDS
DAYS LIVING RADIOISOTOPES
DISEASES
DISPERSIONS
DNA ADDUCTS
DNA REPAIR
HAZARDS
HEALTH HAZARDS
INHALATION
INTAKE
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LUNGS
MAMMALS
NEOPLASMS
NUCLEI
ODD-ODD NUCLEI
ORGANS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
RADIOISOTOPES
RATS
RECOVERY
REPAIR
RESIDUES
RESPIRATORY SYSTEM
RODENTS
SMOKES
SOLS
SYNTHESIS
TOBACCO SMOKES
TRACER TECHNIQUES
VERTEBRATES