Induction of in vivo DNA adducts by 4 industrial by-products in the rat-lung-cell system.
Benz[a]anthracene (BA), dibenz[a,h]anthracene (DBA), dibenzo[a,i]pyrene (DBP), and dibenz[a,h]acridine (DBAC) are by-products found in many industrial wastes and emissions. Workers in the related occupational settings are potentially exposed to these substances through inhalation. In the present study, induction of DNA adducts in vivo by these chemicals was investigated using 32P-postlabeling analysis in the rat-lung-cell system. The potency of DNA-adduct inducing activity was also compared to that of two cytogenetic endpoints i.e., sister-chromatid exchange (SCE) and micronucleus formation. Via intratracheal instillation, male CD rats (6/group) were dosed 3 times with BA, DBA, DBP or DBAC in a 24-h interval. Lung cells were enzymatically separated and used to determine the frequency of DNA adducts, SCE and micronuclei. Results show that all 4 test compounds induced DNA adducts, SCEs, and micronuclei in the rat-lung cell in vivo and that the postlabeling DNA adduct assay detected genotoxic activity at lower dose levels than the two cytogenetic assays. These findings suggest that BA, DBA, DBP or DBAC are rat pulmonary genotoxicants and the DNA-adduct assay is more sensitive than SCE or micronucleus assays for detecting the pulmonary genotoxicity of these industrial PAHs in the in vivo rat-lung-cell system.
Whong
W Z
WZ
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, WV 26505-2888.
Stewart
J D
JD
Cutler
D
D
Ong
T
T
D000166:Acridines / Q000378:metabolism / Q000633:toxicity; D000395:Air Pollutants, Occupational / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism / Q000633:toxicity; D001580:Benzopyrenes / Q000378:metabolism / Q000633:toxicity; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D007220:Industrial Waste / Q000009:adverse effects*; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D008297:Male; D015162:Micronucleus Tests; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D011083:Polycyclic Compounds / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012854:Sister Chromatid Exchange
D000166:Acridines; D000395:Air Pollutants, Occupational; D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; D007220:Industrial Waste; D009153:Mutagens; D011083:Polycyclic Compounds; C022289:dibenzacridine; C021146:dibenzo(a,i)pyrene; D004247:DNA; C030935:benz(a)anthracene; C026486:1,2,5,6-dibenzanthracene