Modulation of m-dinitrobenzene and m-nitrosonitrobenzene toxicity in rat Sertoli--germ cell cocultures

Journal Article · Mon Jan 01 00:00:00 EST 1990 · Fundamental and Applied Toxicology; (USA)

DOI:https://doi.org/10.1016/0272-0590(90)90245-F· OSTI ID:7136179

Cave, D A; Foster, P M ^[1]

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1. Central Toxicology Laboratory, Macclesfield, Cheshire (England)

Previous work has shown that m-dinitrobenzene is a testicular toxicant in rats in vivo, and in vitro produces comparable morphological changes in rat testicular Sertoli-germ cell cocultures. m-Dinitrobenzene is metabolized both in vivo and in the in vitro system to m-nitroaniline m-nitroaniline and m-nitroacetanilide. These metabolites do not provoke testicular toxicity in vivo or in vitro. We have therefore proposed a pathway for the metabolism of m-dinitrobenzene to m-nitroaniline and m-nitroacetanilide, which involved the intermediate m-nitrosonitrobenzene (1-nitroso-3-nitrobenzene, NNB). When tested, m-nitrosonitrobenzene, at equimolar doses to m-dinitrobenzene, produced similar morphological changes in the culture system to those exhibited by m-dinitrobenzene. However, m-nitrosonitrobenzene produced a greater toxicity than did m-dinitrobenzene (as measured by germ cell detachment). When the intracellular thiol levels were reduced in the cocultures pretreated with diethyl maleate, the toxicity of both m-dinitrobenzene and m-nitrosonitrobenzene was enhanced. In contrast, pretreatment of cocultures with agents known to increase cellular thiol (cysteamine) or scavenge reactive intermediates (cysteamine or ascorbate) reduced the toxicity of m-dinitrobenzene and m-nitrosonitrobenzene. We propose that m-dinitrobenzene requires metabolic activation before it can exert its toxicity to Sertoli cells, and it appears that the toxic species is m-nitrosonitrobenzene or a further metabolite of m-nitrosonitrobenzene.

• OSTI ID: 7136179
• Journal Information: Fundamental and Applied Toxicology; (USA), Vol. 14:1; ISSN 0272-0590
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
NITROBENZENE
TOXICITY
NITROSO COMPOUNDS
SPERMATOZOA
SENSITIVITY
ASCORBIC ACID
CELL CULTURES
GLUTATHIONE
MEA
RATS
AMINES
ANIMALS
DRUGS
GAMETES
GERM CELLS
MAMMALS
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RODENTS
THIOLS
VERTEBRATES
VITAMINS
560300* - Chemicals Metabolism & Toxicology