Formation of DNA adducts and induction of mutations in rats treated with tumorigenic doses of 1,6-dinitropyrene

Journal Article · Sat Oct 01 04:00:00 EDT 1994 · Environmental Health Perspectives

DOI:https://doi.org/10.1289/ehp.94102s6185· OSTI ID:478801

Beland, F A; Fullerton, N F; Smith, B A; Heflich, R H ^[1]

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1. National Center for Toxicological Research, Jefferson, AR (United States)

1,6-Dinitropyrene, a component of diesel exhaust, is a lung carcinogen in male F344 rats following a single intrapulmonary administration. In this study, rats were treated with tumorigenic doses of 1,6-dinitropyrene to establish dose-response relationships for the formation of DNA adducts in target (lung) and nontarget (liver) tissues and for the induction of 6-thioguanine-resistant mutations in spleen T-lymphocytes. One week after treatment with 0.3, 1, 3, 10, 30, 100, or 150 {mu}g of 1,6-dinitropyrene, dose-responsive DNA binding was measured in lung and liver with binding in the being 10-fold higher than in the liver. In the lung, a 2-fold increase in dose resulted in a 1.8-fold increase in DNA binding at treatments up to 30 {mu}g of 1,6-dinitropyrene, while in the liver, a 2-fold increase in 1,6-dinitropyrene produced a 2-fold increase in DNA binding at doses up to the 10 {mu}g treatment. Higher doses of 1,6-dinitropyrene resulted in proportionally smaller increases in adduct formation in the two tissues. When measured 21 weeks after treatment, mutations in T-lymphocytes increased with doses up to 100 {mu}g of 1,6-dinitropyrene, but the response was nonlinear throughout the dose range. These findings indicate that concentrations of 1,6-dinitropyrene that produce a dose-dependent induction of lung tumors also result in a dose-dependent formation of DNA adducts and induction of lymphocyte mutations but that the dose-response curves for DNA binding and mutations are different. 39 refs., 3 figs.

• Sponsoring Organization: USDOE
• OSTI ID: 478801
• Report Number(s): CONF-9210376--
• Journal Information: Environmental Health Perspectives, Journal Name: Environmental Health Perspectives Journal Issue: Suppl.6 Vol. 102; ISSN 0091-6765; ISSN EVHPAZ
• Country of Publication: United States
• Language: English

Related Subjects

02 PETROLEUM
55 BIOLOGY AND MEDICINE
BASIC STUDIES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
BIOLOGICAL EFFECTS
COMBUSTION PRODUCTS
CONDENSED AROMATICS
DIESEL FUELS
DNA ADDUCTS
DOSE-RESPONSE RELATIONSHIPS
EXHAUST GASES
GENETIC EFFECTS
INHALATION
LYMPHOCYTES
MUTATIONS
NITRO COMPOUNDS
RATS
RISK ASSESSMENT