METABOLISM AND TESTICULAR TOXICITY OF 1,3-DINITROBENZENE IN THE RAT -EVALUATION OF THE STAGE-SYNCHRONY MODEL

Because many testicular toxicants cause damage to specific stages of s permatogenesis, the present study has investigated the utility of a mo del in which the testis is synchronized to contain only a few closely related spermatogenic stages. The susceptibility of different stages t o 1,3-dinitrobenzene (1,3-DNB) toxicity was investigated in rats, the testes of which had been stage synchronized by a vitamin A depletion/r epletion (VADR) procedure, 1,3-DNB (25 mg/kg, IP) or vehicle was injec ted 58, 61, or 78 d after vitamin A readministration, and testicular h istopathology was evaluated 48 h later, At the time of sacrifice, test es in the three groups were synchronized to stages I-VI, VII-IX, or X- XIV+I, The data indicated that tubules in all stages of spermatogenesi s, in both synchronized and unsynchronized animals, demonstrated histo pathologic changes in response to 1,3-DNB, However, the lesion seen in synchronized animals was more severe and less stage specific than tha t seen in weight-matched, unsynchronized animals, This increase in deg ree of susceptibility could be partially explained by differences in t oxicokinetics, Stage-synchronized testes could provide unique insights into stage-specific cellular and molecular events, especially for in vitro studies where the stage enrichment could be maximally exploited, However, results obtained from in vivo toxicity studies using animals subjected to VADR should be interpreted carefully in light of the con founding physiologic/metabolic perturbations potentially induced by th e VADR procedure. (C) 1997 Elsevier Science Inc.