Carcinogenesis, Vol 18, 193-199, Copyright © 1997 by Oxford University Press
NM Johnsen, PE Schwarze, SH Nyholm, M Lag, R Becher, G Brunborg and JA Holme
The genotoxic effects of the environmental contaminants
benz[j]aceanthrylene (B[j]A), benz[l]aceanthrylene (B[l]A) and
benzo[a]pyrene (B[a]P), and the metabolism of radiolabelled B[j]A, were
studied using rat lung microsomes and various types of isolated rat lung
cells from control and Aroclor 1254 (PCB) treated animals. All three
compounds (10 or 20 microg/plate) resulted in low, but detectable, levels
of His+ revertants in the Salmonella assay when plated with control lung
microsomes. The two cyclopenta polycyclic aromatic hydrocarbons (CP-PAH)
B[j]A and B[l]A, gave increased levels of revertants when plated with
microsomes from PCB-treated animals. Clara cells, type 2 cells and alveolar
macrophages isolated from control rats were exposed to B[j]A, B[l]A or
B[a]P (30 microg/ml, 1 h), but neither of the cell types showed any DNA
damage when measured by alkaline filter elution. However, both B[j]A and
B[l]A (30 microg/ml, 2 h) caused DNA adducts in all three cell types,
measured by the 32P-post- labelling technique, whereas no B[a]P adducts
were detected (30 microg/ml, 2 h). The total DNA adduct levels in Clara
cells, type 2 cells and macrophages exposed to B[j]A were 0.085 +/- 0.033,
0.053 +/- 0.001 and 0.170 +/- 0.030 fmol/microg DNA, respectively, whereas
the total levels in cells exposed to B[l]A were 0.140 +/- 0.070, 0.140 +/-
0.030 and 0.220 +/- 0.080 fmol/microg DNA, respectively. Cells exposed to
B[j]A revealed only one adduct which corresponds with the B[j]A-1,2- oxide
DNA adduct. Judged from high performance liquid chromatography (HPLC)
analysis using radiolabelled B[j]A (30 microg/ml, 30 min), the major
metabolite formed in control microsomes was B[j]A-1,2-diol. Thus, oxidation
at the cyclopenta ring appears to be the most important activation pathway
for B[j]A with control rat lung cells. Exposure of lung cells to CP-PAH (30
microg/ml, 2 h) isolated from PCB pretreated rats resulted in slightly
increased DNA adduct levels in Clara cells and macrophages when compared to
cells isolated from control rats. Furthermore, the adduct pattern had
shifted, and no apparent B[j]A-1,2- oxide adduct could be detected on the
thin layer chromatography (TLC) plate. In contrast, the major metabolite
formed with microsomes from PCB-treated animals was still the
B[j]A-1,2-diol.
ARTICLES
Genotoxic effects of cyclopenta-fused polycyclic aromatic hydrocarbons in different types of isolated rat lung cells
Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway.
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