Genotoxic effects of cyclopenta-fused polycyclic aromatic hydrocarbons in isolated rat hepatocytes and rabbit lung cells

• Published in: Carcinogenesis (New York) 1993-06, Vol.14 (6), p.1125-1131
• Main Authors: Holme, Jørn A., Bjørge, Christine, Søderlund, Erik J., Brunborg, Gunnar, Becher, Rune, Lag, Marit, Schwarze, Per E., Ross, Jeffrey, Nelson, Garret, Nesnow, Stephen
• Format: Article
• Language: English
• Subjects: Animals; Benz(a)Anthracenes - toxicity; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; DNA - drug effects; DNA Damage; DNA Repair; Liver - drug effects; Liver - ultrastructure; Lung - drug effects; Lung - ultrastructure; Male; Medical sciences; Methylcholanthrene - analogs & derivatives; Methylcholanthrene - toxicity; Mutagenicity Tests; Mutagens - toxicity; Rabbits; Rats; Rats, Wistar; Tumors
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/14.6.1125

Benz[j]aceanthrylene (B[j]A) and benz[l)aceanthrylene (B[l]A), two isomeric cyclopenta polycyclic aromatic hydrocarbons (CP-PAH) structurally related to 3-methylcholanthrene, were studied with respect to their genotoxic effects in isolated liver and lung cells. Both compounds were found to cause DNA adducts measured by the 32P-postlabelling technique. The level of DNA-adducts in rat hepatocytes exposed to 30 μg/ml B[l]A and B[j]A for 4 h were 46.5 ± 22.0 and 8.3 ± 5.1 fmol/μg DNA respectively. Using butanol extractions, the major and one of the minor B[l] A adducts co-chromatographed with B[j]A-l, 2-oxide adducts of 2'-deoxyadenosine and 2'-deoxyguanosine. Thus, oxidation at the cyclopenta-ring of B[j]A appears to be an important activation pathway. In hepatocytes, 3-30 μg/ml of B[j]A and B[j]A induced DNA damage and repair measured both as increased alkaline elution of DNA and as increased incorporation of [3H]TdR in the DNA. B[l]A was somewhat more potent than B[j]A in inducing DNA repair. Reactive CP-PAH intermediates formed in the hepatocytes caused mutations in Salmonella typhimurium TA98 upon co-incubation. DNA adducts were also observed in isolated rabbit lung cells exposed to 30 μg/ml B[l]A or B[j]A for 2 h. A total of 14.5 ± 6.9, 2.9 ± 2.1 and 0.2 ± 0.6 fmol B[l] A adducts/μg DNA were observed in Clara cells, type II pneumocytes and alveolar macrophages respectively. The main B[l]A adduct observed in the liver cells was not found in the lung cells. On the other hand, the levels of B[j]A adducts in the lung cells were in the range 4-14% of that found in liver cells, and no major differences between the various lung cells were observed. Neither B[l]A nor B[j]A induced DNA damage measured by alkaline elution in the lung cells, indicating that these adducts are not alkali labile.