DNA adducts in hamster and rat tracheas exposed to benzo(a)pyrene in vitro.
Syrian golden hamsters are much more susceptible than Wistar rats to the induction of tracheal tumors by benzo(a)pyrene (BP). In order to investigate whether this difference is reflected in the pattern of DNA-adduct induction and removal, tracheas from either species were isolated and exposed to BP (5 micrograms/ml) in organ culture. At various time-points BP-DNA adducts in the epithelial cells were quantified by 32P-postlabeling; unscheduled DNA synthesis (UDS) was determined by [3H]thymidine incorporation. In an induction-repair experiment tracheas were exposed to BP for 2 days, and cultured for another 4 days without BP. After 2 days of exposure total BP-DNA adduct levels were 10 times higher in hamster compared to rat tracheas. In hamster tracheas one major adduct was formed (95%), vs. the adduct between (+)-anti-BP-diolepoxide and deoxyguanosine (BPDE-N2dG). In rat tracheas BPDE-N2dG comprised about 60% of the total adduct level. During exposure to BP the adduct level in hamster trachea increased to 36 +/- 19 adducts/10(6) nucleotides (add/10(6) n) on day 2. Two days after removal of BP the BP-DNA adduct level had decreased to 60% of that on day 2; there was no further decrease in the BP-DNA adduct level. UDS increased during exposure to BP and decreased after removal of BP. In rats, removal of BP did not lead to a decrease in the BP-DNA adduct level, which agreed with the observed absence of UDS. In a second experiment tracheas were exposed to BP continuously for 15 days. In hamster tracheas the total BP-DNA adduct level increased from 11 +/- 0.7 add/10(6) n after 1 day of exposure to 105 +/- 2 add/10(6) n after 15 days; also UDS increased with increasing exposure until day 11. In rat tracheas no progressive increase in the BP-DNA adduct level was seen. It was concluded that the difference in trachea tumor susceptibility between hamsters and rats exposed to BP correlates with the difference between the 2 species in BP-DNA adduct kinetics in the trachea epithelial cells.
Roggeband
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TNO Medical Biological Laboratory, Department of Genetic Toxicology, Rijswijk, The Netherlands.
Wolterbeek
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AP
van den Berg
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PT
Baan
R A
RA
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000378:metabolism* / Q000633:toxicity*; D006224:Cricetinae; D046508:Culture Techniques; D004247:DNA / Q000187:drug effects* / Q000378:metabolism*; D018736:DNA Adducts; D004260:DNA Repair; D008297:Male; D008647:Mesocricetus; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism*
D002274:Carcinogens, Environmental; D018736:DNA Adducts; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; D004247:DNA