R. Roggeband et al., DNA ADDUCT FORMATION AND REPAIR IN HAMSTER AND RAT TRACHEAS EXPOSED TO BENZO[A]PYRENE IN ORGAN-CULTURE, Carcinogenesis, 15(4), 1994, pp. 661-665
Syrian golden hamsters are much more susceptible than Wistar rats to t
he induction of tracheal tumors by benzo[a]pyrene (B[a]P). To investig
ate whether this difference is reflected in the pattern of DNA adduct
induction and removal, tracheas from either species were isolated and
exposed to B[a]P (5 mu g/ml) in organ culture. At various time-points
B[a]P-DNA adducts were quantified by (32)p- postlabeling; unscheduled
DNA synthesis (UDS) and cell proliferation were determined by [H-3]thy
midine incorporation during the 18 h before sampling. In an induction-
repair experiment tracheas were exposed to B[a]P for 2 days, and cultu
red for another 4 days without B[a]P. After 2 days of exposure total B
[a]P-DNA adduct levels were 10 times higher in hamster compared to rat
tracheas. In hamster tracheas one major adduct was formed (95%), name
ly the adduct between (+)-anti-benzo[a]pyrene diolepoxide and deoxygua
nosine (BPDE-N(2)dG). In rat tracheas BPDE-N(2)dG comprised similar to
60% of the total B[a]P-DNA adduct level. The other major adduct found
in rat tracheas is probably derived from interaction of syn-BPDE and
deoxyadenosine. During exposure to B[a]P in hamsters the adduct level
increased to 36 +/- 19 adducts/10(6) nucleotides (add/10(6)n) on day 2
. Two days after removal of B[a]P the B[a]P-DNA adduct level had decre
ased to 60% of that on day 2; there was no further decrease in the B[a
]P-DNA adduct level, despite considerable cell proliferation at the en
d of the 6 day culture period. UDS increased during exposure to B[a]P
and decreased after removal of B[a]P. In rats removal of B[a]P did not
lead to a decrease in the B[a]P-DNA adduct level, which agreed with t
he observed absence of UDS. In a second experiment tracheas were expos
ed to B[a]P continuously for 15 days. In hamster tracheas the total B[
a]P-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. Cell proliferation was low at t
he end of the culture period. In rat tracheas no progressive increase
in the B[a]P-DNA adduct level was seen, UDS was not increased and cell
proliferation had increased significantly at the end of the exposure
period. The extent of adduct induction in the trachea of the two speci
es corresponded with the different susceptibilities to B[a]P-induced t
umor formation.