ADENOMAS INDUCED BY POLYCYCLIC AROMATIC-HYDROCARBONS IN STRAIN A J MOUSE LUNG CORRELATE WITH TIME-INTEGRATED DNA ADDUCT LEVELS/

The induction of DNA adducts and adenomas in the lungs of strain A/J m ice has been investigated following the single i.p. administration of each of the following polycyclic aromatic hydrocarbons (PAH): pyrene, dibenz[a,h]anthracene, benzo[a]pyrene, benzo[b]fluoranthene, 5-methylc hrysene, and cyclopenta[c,d]pyrene. DNA adducts were measured by P-32- postlabeling at times between 1 and 21 days following injection, while adenomas were counted at 240 days after treatment. Pyrene did not ind uce either DNA adducts or lung adenomas at any of the doses examined. Each of the remaining PAH induced both adenomas and DNA adducts in a d ose-dependent manner, with dibenz[a,h]anthracene > 5-methylchrysene > cyclopenta[c,d]pyrene > benzo[a]pyrene > benzo[b]fluoranthene. DNA add ucts reached maximal levels between 3 and 9 days after injection, foll owed by a gradual decrease. The time-integrated DNA adduct level (TIDA L) was calculated by numerically integrating the areas under the adduc t persistence curves extrapolated to 240 days for each PAR at each dos e Level. This value represents the effective total molecular dose of P AH that was delivered to the lung DNA over the entire course of tumori genesis. A strong correlation of lung adenoma induction with the TIDAL values was observed for each PAH. The slopes of the tumors versus TID AL value relationships were essentially identical for 5-methylchrysene , cyclopenta[cd]pyrene, benzo[a]pyrene, and benzo[b]fluoranthene. The slope of this relationship for dibenz[a,h]anthracene was markedly grea ter. The essentially identical induction of adenomas as a function of TIDAL values for these PAR suggests that the formation and persistence of DNA adducts determines their carcinogenic potency.