Genotoxic effects of cyclopenta-fused polycyclic aromatic hydrocarbons in isolated rat hepatocytes and rabbit lung cells.
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 micrograms/ml B[l]A and B[j]A for 4 h were 46.5 +/- 22.0 and 8.3 +/- 5.1 fmol/micrograms DNA respectively. Using butanol extractions, the major and one of the minor B[j]A adducts co-chromatographed with B[j]A-1,2-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 micrograms/ml of B[j]A and B[l]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 micrograms/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/micrograms 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.
Holme
J A
JA
Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway.
Bjørge
C
C
Søderlund
E J
EJ
Brunborg
G
G
Becher
R
R
Lag
M
M
Schwarze
P E
PE
Ross
J
J
Nelson
G
G
Nesnow
S
S
D000818:Animals; D001551:Benz(a)Anthracenes / Q000633:toxicity*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair; D008099:Liver / Q000187:drug effects* / Q000648:ultrastructure; D008168:Lung / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008748:Methylcholanthrene / Q000031:analogs & derivatives* / Q000633:toxicity; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
D001551:Benz(a)Anthracenes; D009153:Mutagens; D008748:Methylcholanthrene; C041193:benz(l)aceanthrylene; C037411:benz(j)aceanthrylene; D004247:DNA