Activity of carcinogens, carcinogen analogs, and metabolic inhibitors in the lymphocyte tritiated thymidine assay.

Inhibition of tritiated thymidine ([3H]dThd) incorporation into replicating DNA of concanavalin A (Con A)-stimulated C57BL/6J splenic lymphocytes has been further evaluated as an end point for rapid in vitro discrimination between carcinogenic and noncarcinogenic chemicals. Results of this evaluation include: a) Inhibition of [3H]dThd incorporation into DNA of Con A-stimulated cells clearly discriminated between known DNA-damaging chemical carcinogens (N-methyl-N-nitrosourea, 4-nitroquinoline 1-oxide, 4-(hydroxyamino)quinoline 1-oxide, benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, and benz[a]anthracene) and non-DNA-damaging metabolic inhibitors of replication (dimethyl sulfoxide, ethanol, hydroxyurea, cycloheximide, potassium cyanide, and oligomycin). b) Inhibition of [3H]dThd incorporation also discriminated between carcinogens and noncarcinogens in the two pairs 4-nitroquinoline 1-oxide versus quinoline-N-oxide, and benzo[a]pyrene versus pyrene. c) Inhibition of [3H]dThd incorporation did not quantitatively discriminate between the structurally related strong carcinogen dimethylbenz[a]anthracene, the weak carcinogen benz[a]anthracene, and the equivocal carcinogens anthracene and phenanthrene. d) Inhibition of [3H]dThd incorporation was not a sensitive in vitro end point for the carcinogenic hypolipidemic drug 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (Wy-14,643).