DNA adduct formation in rat alveolar type II cells: cells potentially at risk for inhaled diesel exhaust.
Diesel exhaust (DE) is a pulmonary carcinogen in rats. One potential mechanism for DE-induced carcinogenicity involves the interaction of the organic chemicals associated with DE soot with DNA in target cells. The purpose of this study was to determine whether peripheral lung cells, specifically alveolar type II cells, are at risk from inhaled DE. Rats were exposed 16 hr/day, 5 days/week to filtered air (controls), carbon black (CB) (6.2 mg/m3), or to diluted DE (6.2 mg/m3) for 12 weeks. CB particles were used for comparison with DE soot, because the CB particles are morphologically similar to soot particles, but are virtually devoid of adsorbed organic compounds. Type II alveolar cells were isolated by flow cytometry and DNA in the cells was analyzed for DNA adducts using the 32P-postlabeling assay. There was a significant increase (approximately 4-fold) in the level of total adducts in type II cells of rats exposed to DE and CB, compared with sham-exposed rats. While exposure to CB and DE induced the formation of adducts that were not consistently seen in sham-exposed rats, exposure to these materials also appeared to increase the intensity of adducts present in type II cells from sham-exposed rats. These data underscore the importance of investigating molecular dosimetry at the biological level of the cell. We conclude that the type II alveolar cell may be a risk for damage from inhaled DE.
Bond
J A
JA
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico.
Johnson
N F
NF
Snipes
M B
MB
Mauderly
J L
JL
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001273:Atmosphere Exposure Chambers; D002244:Carbon / Q000494:pharmacology*; D002273:Carcinogens; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005740:Gases / Q000633:toxicity*; D066298:In Vitro Techniques; D001239:Inhalation; D008297:Male; D010578:Petroleum / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012307:Risk Factors
D002273:Carcinogens; D005740:Gases; D010578:Petroleum; D002244:Carbon; D000255:Adenosine Triphosphate; D004247:DNA