3,4-DICHLOROPROPIONANILIDE-INDUCED ATROPHY OF THE THYMUS - MECHANISMSOF TOXICITY AND RECOVERY

The herbicide 3,4-dichloropropionanilide (propanil) has several well-d ocumented neurotoxic and immunotoxic effects on mice. We report here a detailed characterization of the effects of propanil exposure on the thymus. We found that at doses of 100-200 mg/kg, propanil induces sign ificant thymic atrophy between 2 and 7 days postexposure, This atrophy is characterized by a decrease in thymus/body ratio and a decrease in cellularity. Flow cytometric analyses of thymuses from propanil- and vehicle-treated mice indicate that the CD4(+) CD8(+) population of imm ature cells, is most significantly decreased in propanil-exposed mice. We performed cell cycle analysis of thymocyte populations using two-c olor surface staining and the DNA binding dye 7-aminoactinomycin D to determine whether thymic atrophy was associated with changes in the pe rcentages of cells in the S, G(2), and M phases of the cell cycle. We found a high percentage of proliferating CD4(+)CD8(+) thymocytes 4 day s after exposure. Thus, recovery of the thymus occurs following increa ses in thymocyte proliferation, most notably the immature CD4(+) CD8() thymocytes. We tested the hypothesis that glucocorticoids play a rol e in the observed atrophy by examining thymuses in adrenalectomized, p ropanil-treated mice. No atrophy was observed in those animals. These results suggest that propanil has an immunotoxic effect on the thymus that appears to be mediated, in part, by endogenous glucocorticoids. ( C) 1996 Society of Toxicology