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]pyren e (DBP), and dibenz[a,h]acridine (DBAC) are by-products found in many industrial wastes and emissions. Workers in the related occupational s ettings are potentially exposed to these substances through inhalation . In the present study, induction of DNA adducts in vivo by these chem icals was investigated using P-32-postlabeling analysis in the rat-lun g-cell system. The potency of DNA-adduct inducing activity was also co mpared to that of two cytogenetic endpoints i.e., sister-chromatid exc hange (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 t o determine the frequency of DNA adducts, SCE and micronuclei. Results show that all 4 test compounds induced DNA adducts, SCEs, and micronu clei in the rat-lung cell in vivo and that the postlabeling DNA adduct assay detected genotoxic activity at lower dose levels than the two c ytogenetic assays. These findings suggest that BA, DBA, DBP or DBAC ar e rat pulmonary genotoxicants and the DNA-adduct assay is more sensiti ve than SCE or micronucleus assays for detecting the pulmonary genotox icity of these industrial PAHs in the in vivo rat-lung-cell system.