Benzene Adducts with Rat Nucleic Acids and Proteins: Dose-Response Relationship after Treatment In Vivo

• Published in: Environmental health perspectives Vol. 82; pp. 259 - 266
• Main Authors: Mazzullo, Mario, Bartoli, Silvana, Bonora, Bruna, Colacci, Annamaria, Grilli, Sandro, Lattanzi, Giovanna, Niero, Alessandra, Turina, Maria Paola, Parodi, Silvio
• Format: Journal Article
• Language: English
• Published: United States National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare 01-07-1989
• Subjects: 550201 - Biochemistry- Tracer Techniques; 560300 - Chemicals Metabolism & Toxicology; ADDUCTS; Animals; AROMATICS; BASIC BIOLOGICAL SCIENCES; BENZENE; Benzene - metabolism; BODY; CARBON 14 COMPOUNDS; CARCINOGENESIS; CHEMICAL REACTIONS; Chromatography, High Pressure Liquid; CROSS-LINKING; DIGESTIVE SYSTEM; DNA; DNA - metabolism; DNA ADDUCTS; Dosage; Dose response relationship; Dose-Response Relationship, Drug; DOSE-RESPONSE RELATIONSHIPS; Full-Length Manuscripts from Poster Session; GASTROINTESTINAL TRACT; GLANDS; HYDROCARBONS; HYDROGEN COMPOUNDS; INJECTION; INTAKE; INTRAPERITONEAL INJECTION; Kidney - metabolism; LABELLED COMPOUNDS; LIVER; Liver - metabolism; Lung - metabolism; Lungs; Macromolecules; Male; NUCLEIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PATHOGENESIS; POLYMERIZATION; Protein Binding; PROTEINS; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; Rats; Rats, Inbred Strains; RNA; RNA - metabolism; SPLEEN; Spleen - metabolism; STOMACH; Stomach - metabolism; Tissue Distribution; TRITIUM COMPOUNDS
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.8982259

The dose-response relationship of the benzene covalent interaction with biological macromolecules from rat organs was studied. The administered dose range was 3.6× 107starting from the highest dosage employed, 486 mg/kg, which is oncogenic for rodents, and included low and very low dosages. The present study was initially performed with tritium-labeled benzene, administered by IP injection. In order to exclude the possibility that part of the detected radioactivity was due to tritium incorporated into DNA from metabolic processes,14C-benzene was then also used following a similar experimental design. By HPLC analysis, a single adduct from benzene-treated DNA was detected; adduct identification will be attempted in the near future. Linear dose-response relationship was observed within most of the range of explored doses. Linearity was particularly evident within low and very low dosages. Saturation of benzene metabolism did occur at the highest dosages for most of the assayed macromolecules and organs, especially in rat liver. This finding could be considered as indicative of the dose-response relationship of tumor induction and could be used in risk assessment.