In vitro toxicity of 1,2-dibromo-3-chloropropane to isolated testicular cells
The biochemical basis for the antispermatogenic properties of 1,2-dibromo-3-chloropropane (DBCP) was studied using hepatic and testicular mitochondria, as well as Sertoli cells and primary spermatocytes isolated from immature rats. Pyruvate-supported mitochondrial respiration was inhibited by DBCP with an ED/sub 50/ of 0.19 ..mu..mol/mg protein. Lactate production by cultured Sertoli cells was stimulated by 0.5-2.0 mM DBCP from 17-62% above that obtained with 1 ..mu..g/ml follicle stimulating hormone. Exposure of Sertoli cells to 0.5-2.0 mM DBCP also increased the specific activity of lactate dehydrogenase (LDH) from 18-35% above control. Aerobic /sup 14/C-lactate metabolism by spermatocytes was inhibited by 1.0-2.0 mM DBCP as demonstrated by /sup 14/C-CO/sub 2/ production that was 65-89% less than control. These data support the hypothesis that DBCP, by virtue of its disruptive effect on mitochondria, is selectively cytotoxic to immature germ cells due to their dependence on aerobic energy metabolism. DBCP, at a dose of 0.5 ..mu..mol/10/sup 16/ cells, was 3 times more cytotoxic to spermatocytes than epichlorohydrin (ECH), and 9 times more cytotoxic than 1,2-dibromoethane (EDB). These data argue against the involvement of ECH and ACH in DBCP-induced testicular toxicity, and further indicate that mitochrondrial dysfunction may disrupt spermatogenesis. Glutathione S-transferases (GST) in hepatic, renal, and testicular cytosol catalyzed glutathione (GSH) conjugation to DBCP with tissue-specific K/sub m/ and V/sub max/ values. This reaction did not enhance the mutagenicity of DBCP in the Ames assay. Mutagenic activation was produced by S9 or microsomal enzymes in the presence of NADPH, and was partially inhibited by GSH.
- Research Organization:
- Michigan Univ., Ann Arbor (USA)
- OSTI ID:
- 6785134
- Country of Publication:
- United States
- Language:
- English
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560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOCHEMISTRY
BODY
CARBON 14 COMPOUNDS
CELL CONSTITUENTS
CHEMISTRY
CHLORINATED ALIPHATIC HYDROCARBONS
DIGESTIVE SYSTEM
GERM CELLS
GLANDS
GONADS
HALOGENATED ALIPHATIC HYDROCARBONS
IN VITRO
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
MALE GENITALS
MAMMALS
METABOLISM
MITOCHONDRIA
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANOIDS
ORGANS
RATS
RODENTS
SPERMATOCYTES
TESTES
TOXICITY
TRACER TECHNIQUES
VERTEBRATES