The human testicular toxicant
1,2-dibromo-3-chloropropane (
DBCP) was studied for the same end-point in 4 different species of laboratory animals. Marked
necrosis and
atrophy of the seminiferous epithelium were observed in rats and guinea pigs 10 days after a single i.p. administration of
DBCP (170-340 mumol/kg), whereas significantly less damage was observed in hamsters and mice. The testicular concentrations of
DBCP measured at various time-points after the i.p. injection of
DBCP indicated that factors in addition to tissue concentration were of importance for the observed species differences in sensitivity towards
DBCP-induced testicular damage. Also, there did not seem to be any direct correlation between
DBCP-induced in vivo testicular toxicity and in vitro GSH-dependent dehalogenation, inasmuch as the rate of
bromide release from
DBCP with hamster testicular cytosol was as fast as that with rat cytosol. Testicular DNA damage, as determined by alkaline elution 60 min after in vivo administration of 170 mumol/kg
DBCP, was observed only in rats and guinea pigs. Thus, induction of DNA damage correlates with the relative susceptibilities of the species towards
DBCP-induced testicular
necrosis. To further study species differences in testicular activation of
DBCP to
DNA-damaging intermediate(s), cells isolated from the testes of the 4 species were incubated with
DBCP. Testicular cells from rats and guinea pigs were the only preparations developing substantial DNA damage after 60 min incubation with low concentrations of
DBCP (5-50 microM). The findings indicate that rats are sensitive towards
DBCP-induced testicular
necrosis because rat testicular cells easily activate
DBCP to
a DNA-damaging intermediate(s). The relative high testicular
DBCP concentration as well as the ability to activate
DBCP may explain the sensitivity of guinea pigs towards
DBCP-induced testicular toxicity.