Damage of proliferating lymphoid cell deoxyribonucleic acid by methyl methanesulfonate and N-acetoxy-2-acetylaminofluorene.

Replicative synthesis of deoxyribonucleic acid by splenic lymphoid cells cultured from C57BL/6J strain mice and stimulated to proliferate with concanavalin A (Con A) was strongly suppressed by short exposure (10-60 min) of the cells to the direct-acting carcinogens methyl methanesulfonate or N-acetoxy-2-acetylaminofluorene. Carcinogen-treated lymphoid cells failed to recover stimulated levels of replicative synthesis after incubation for several hours in fresh medium without carcinogen. In contrast, spleen cells treated with hydroxyurea (a metabolic inhibitor of deoxyribonucleic acid replication) fully recovered stimulated rates of replicative synthesis upon incubation in medium without hydroxyurea. Furthermore, the inhibition of replicative synthesis by the carcinogens was accompanied by marked stimulation of deoxyribonucleic acid repair synthesis. Concomitant measurement of replicative and repair synthesis appears to be an effective approach for the in vitro study of carcinogen-induced damage in the deoxyribonucleic acid of proliferating lymphoid cells.