Toxicity and metabolism of 1,3-dinitrobenzene in rat testicular cell cultures
P M Foster1, S C Lloyd, M S Prout
1Biochemical Toxicology Section, Central Toxicology Laboratory, Imperial Chemical Industries plc, Alderley Park, Nr Macclesfield, Cheshire SK10 4TJ, England.
Abstract:
The testicular toxicity of 1,3-dinitrobenzene (DNB) has been modelled in primary cultures of rat testis. The morphological response obtained in vitro following direct addition of the compound to the cultures was analogous to that seen in vivo. This was characterized by Sertoli cell vacuolation and germ cell detachment. The effect could be quantified using germ cell exfoliation into the culture medium, with a significant response occurring at toxicologically relevant concentrations of DNB (5 x 10(-6)m and above). Both Sertoli-germ cell co-cultures and Sertoli cell cultures were shown to be capable of xenobiotic metabolism, with nitroreduction of DNB being the predominant route. It is postulated that DNB or a Sertoli cell metabolite (probably an intermediate of nitroreduction produced in situ) is responsible for the testicular damage observed following administration of the compound in vivo.
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