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 t he induction of tracheal tumors by benzo(a)pyrene (BP). In order to in vestigate whether this difference is reflected in the pattern of DNA-a dduct induction and removal, tracheas from either species were isolate d and exposed to BP (5 mu g/ml) in organ culture. At various time-poin ts BP-DNA adducts in the epithelial cells were quantified by P-32-post labeling; unscheduled DNA synthesis (UDS) was determined by [H-3]thymi dine incorporation. In an induction-repair experiment tracheas were ex posed to BP for 2 days, and cultured for another 4 days without BP. Af ter 2 days of exposure total BP-DNA adduct levels were 10 times higher in hamster compared to rat tracheas. In hamster tracheas one major ad duct was formed (95%), vs. the adduct between (+)-anti-BP-diolepoxide and deoxyguanosine (BPDE-N(2)dG). In rat tracheas BPDE-N(2)dG comprise d about 60% of the total adduct level. During exposure to BP the adduc t level in hamster trachea increased to 36 +/- 19 adducts/10(6) nucleo tides (add/10(6)n) on day 2. Two days after removal of BP the BP-DNA a dduct level had decreased to 60% of that on day 2; there was no furthe r decrease in the BP-DNA adduct level. UDS increased during exposure t o 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 a dduct level increased from 11 +/- 0.7 add/10(6)n after 1 day of exposu re to 105 +/- 2 add/10(6)n after 15 days; also UDS increased with incr easing exposure until day 11. In rat tracheas no progressive increase in the BP-DNA adduct level was seen. It was concluded that the differe nce in trachea tumour 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.