Formation and removal of DNA adducts in Fischer-344 rats exposed to 2,4-diaminotoluene. 1994

D K La, and J R Froines
Department of Environmental Health Sciences, University of California, Los Angeles 90024.

32P-Postlabeling was used to examine DNA adduct formation and removal in Fischer-344 rats exposed to the animal carcinogen 2,4-diaminotoluene (DAT). Adduct formation and persistence were compared between target (liver and mammary gland) and non-target organs (kidney and lung) to determine if possible differences could explain the observed organ specificity of DAT induced carcinogenesis. The effects of different exposure conditions on DNA adduct formation and removal were also examined by varying the concentration and frequency of compound administration. DAT produced three distinct DNA adducts. Among the organs examined, DNA binding was highest in the liver, with levels approximately 10 times greater than that of the mammary gland and up to 50 times greater than of the two nontarget sites. Despite the large differences in the initial extent of adduct formation, the persistence of adducts among sites was not significantly different. In the liver, there were dose-dependent differences in DNA adduct formation, but adduct removal following different dosages did not vary significantly. The effects of multiple administration on DNA adduct formation and removal were examined by treating rats with 5 mg/kg DAT daily for 10 consecutive days. Adduct yields from multiple treatment were greater than from a single 50 mg/kg exposure. The persistence of adducts following multiple treatment was also greater than after an equivalent single exposure. The results demonstrated organ-specific and dose-dependent differences in initial extent of DNA adduct formation, but no differences in adduct persistence. However, the results did suggest that adduct formation and persistence may change with repeated administration of DAT.

UI MeSH Term Description Entries
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008321 Mammary Glands, Animal MAMMARY GLANDS in the non-human MAMMALS. Mammae,Udder,Animal Mammary Glands,Animal Mammary Gland,Mammary Gland, Animal,Udders
D010655 Phenylenediamines Aniline compounds that contain two amino groups. They are used as a precursor in the synthesis of HETEROCYCLIC COMPOUNDS and POLYMERS. p-Phenylenediamine is used in the manufacture of HAIR DYES and is an ALLERGEN.
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D002855 Chromatography, Thin Layer Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Chromatography, Thin-Layer,Thin Layer Chromatography,Chromatographies, Thin Layer,Chromatographies, Thin-Layer,Thin Layer Chromatographies,Thin-Layer Chromatographies,Thin-Layer Chromatography
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses

Related Publications

D K La, and J R Froines
March 1993, Xenobiotica; the fate of foreign compounds in biological systems,
D K La, and J R Froines
November 1989, Fundamental and applied toxicology : official journal of the Society of Toxicology,
D K La, and J R Froines
May 1989, Toxicology and industrial health,
D K La, and J R Froines
January 1989, Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement,
Copied contents to your clipboard!