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

Journal Article · Tue Dec 01 04:00:00 EST 1987 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(87)90058-5· OSTI ID:5466803

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

Selectively deuterated and methylated analogs of the nematocide 1,2-dibromo-3-chloropropane (DBCP) were compared to DBCP in causing acute renal damage in rats. All of the six deuterated analogs tested at 340 mumol/kg, including the perdeutero compound, failed to significantly alter the kidney necrosis observed at 48 hr compared to DBCP. Furthermore, when the perdeutero analog was administered at several doses (42.5, 85, 170, and 340 mumol/kg), it caused kidney damage that was not significantly different than that caused by an equivalent molar dose of nondeuterated DBCP. Of the five methylated analogs tested at 170 and 340 mumol/kg, only C3-methyl-DBCP and 1,2-dibromo-4-chlorobutane caused nephrotoxicity. The C2-methyl-, C1-dimethyl-, and C2-methyl-DBCP analogs failed to cause renal necrosis determined 48 hr after dosing. In distribution studies DBCP, perdeutero-DBCP, and all the methylated analogs were found to concentrate in the kidney approximately 25 times relative to plasma 1 hr after administration. DBCP at doses of 4.3 mumol/kg and higher caused DNA damage in the kidney as early as 10 min after administration, as measured by alkaline elution of DNA from isolated kidney nuclear preparations. Perdeuteration did not decrease the DNA damaging effect of DBCP. The ability of the methylated DBCP analogs to induce renal DNA damage correlated with their necrogenic potential. Experiments using pretreatments that are known to decrease the nephrotoxicity caused by glutathione and cysteine conjugates of several halogenated alkenes were conducted to examine the effect of these pretreatments on DBCP-induced nephrotoxicity.

• Research Organization: National Institute of Public Health, Oslo, Norway
• OSTI ID: 5466803
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 91:3; ISSN TXAPA
• 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.
ALKANES
ANIMALS
BIOLOGICAL EFFECTS
BODY
CHEMICAL REACTIONS
DEUTERIUM
DNA
DRUGS
GENETIC EFFECTS
GLUTATHIONE
HALOGENATED ALIPHATIC HYDROCARBONS
HYDROCARBONS
HYDROGEN ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KIDNEYS
LIGHT NUCLEI
MAMMALS
METHYLATION
NECROSIS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PEPTIDES
POLYPEPTIDES
PROPANE
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
STABLE ISOTOPES
TOXICITY
TRACER TECHNIQUES
VERTEBRATES