Testicular necrosis and DNA damage caused by deuterated and methylated analogs of 1,2-dibromo-3-chloropropane in the rat

Journal Article · Fri Jul 01 00:00:00 EDT 1988 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(88)90284-0· OSTI ID:7069977

Soderlund, E J; Brunborg, G; Omichinski, J G; Holme, J A; Dahl, J E; Nelson, S D; Dybing, E

To study the role of metabolism in 1,2-dibromo-3-chloropropane (DBCP)-induced testicular damage in rats, selectively deuterated and methylated analogs of DBCP were given as a single ip dose of 340 mumol/kg and testicular toxicity was determined 10 days after treatment. None of the four deuterated analogs C1-D2-, C2-D1-, C3-D2-, or C1-C2-C3-D5-DBCP reduced the degree of testicular damage compared to DBCP, indicating that metabolic cleavage of a C-H bond was not rate-limiting in DBCP-induced testicular toxicity. Of the five methylated analogs, C1-methyl-, C1-dimethyl-, C2-methyl-, and C3-methyl-DBCP and 1,2-dibromo-4-chlorobutane, only C3-methyl-DBCP caused testicular toxicity. DBCP treatment resulted in increased testicular DNA damage at doses of 85-170 mumol/kg as measured by alkaline elution of DNA from testicular cells isolated 3 hr after in vivo treatment. The perdeutero-DBCP analog induced testicular DNA damage that was at least as extensive as that induced by DBCP. Of the methylated analogs tested, only C3-methyl-DBCP gave a marked dose-dependent increase in testicular DNA damage between 170 and 540 mumol/kg. There were no significant differences in the testicular tissue distribution between DBCP, perdeutero-DBCP, and the methylated DBCP analogs. Furthermore, in distribution studies with DBCP, C1-methyl- and C3-methyl-DBCP, and 1,2-dibromo-4-chlorobutane, the highest tissue concentrations were found in the kidneys, followed by the liver and then the testes. The fact that testicular DNA damage of DBCP and its deuterated and methylated analogs paralleled their ability to cause testicular necrosis and atrophy makes measurement of DNA damage a very useful correlate in mechanistic studies of DBCP-induced testicular cell death.

• Research Organization: National Institute of Public Health, Oslo (Norway)
• OSTI ID: 7069977
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 94:3; ISSN TXAPA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKANES
ANIMALS
AROMATICS
BIOLOGICAL EFFECTS
BODY
CHEMICAL REACTIONS
CHLORINATED AROMATIC HYDROCARBONS
DEUTERIUM
DISTRIBUTION
DNA
DOSE-RESPONSE RELATIONSHIPS
GENETIC EFFECTS
GONADS
HALOGENATED AROMATIC HYDROCARBONS
HYDROCARBONS
HYDROGEN ISOTOPES
IN VITRO
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MALE GENITALS
MAMMALS
METHYLATION
NECROSIS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PROPANE
RATS
RODENTS
STABLE ISOTOPES
TESTES
TISSUE DISTRIBUTION
TOXICITY
TRACER TECHNIQUES
VERTEBRATES