DNA adducts and carcinogenicity of nitro-polycyclic aromatic hydrocarbons

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

DOI:https://doi.org/10.1289/ehp.94102s6177· OSTI ID:478800

Fu, P P; Herreno-Saenz, D; Von Tungeln, L S ^[1]

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

We have been interested in the structure-activity relationships of nitro-polycyclic aromatic hydrocarbons (nitro-PAHs), and have focused on the correlation of structural and electronic features with biological activities, including mutagenicity and tumorigenicity. In our studies, we have emphasized 1-, 2-, 3-, and 6-nitrobenzo[a]pyrenes (nitro-B[a]Ps) and related compounds, all of which are derived from the potent carcinogen benzo[a]pyrene. While 1-, 2-, and 3-nitro-B[a]P are potent mutagens in Salmonella, 6-nitro-B[a]P is a weak mutagen. In vitro metabolism of 1- and 3-nitro-B[a]P has been found to generate multiple pathways for mutagenic activation. The formation of the corresponding trans-7,8-dihydrodiols and 7,8,9,10-tetrahydrotetrols suggests that 1- and 3-nitro-B[a]P trans-7,8-diol-anti-9, 10--epoxides are ultimate metabolites of the parent nitro-B[a]Ps. We have isolated a DNA adduct from the reaction between 3-nitro-B[a]P trans-7,8-diol-anti-9, 10-epoxide and calf thymus DNA, and identified it as 10-(deoxyguanosin-N{sup 2}-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-3-nitro-B[a]P. The same adduct was identified from in vitro metabolism of [{sup 3}H]3-nitro-B[a]P by rat liver microsomes in the presence of calf thymus DNA. A DNA adduct of 3-nitro-B[a]P formed from reaction of N-hydroxy-3-amino-B[a]P, prepared in situ with calf thymus DNA was also isolated. This adduct was identified as 6-(deoxyguanosin-N{sup 2}-yl)-3-amino-B[a]P. The same adduct was obtained from incubating DNA with 3-nitro-B[a]P in the presence of the mammalian nitroreductase, xanthine oxidase, and hypoxanthine. 48 refs., 6 figs., 1 tab.

• Sponsoring Organization: USDOE
• OSTI ID: 478800
• Report Number(s): CONF-9210376--
• Journal Information: Environmental Health Perspectives, Journal Name: Environmental Health Perspectives Journal Issue: Suppl.6 Vol. 102; ISSN EVHPAZ; ISSN 0091-6765
• 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
EXHAUST GASES
HYPOXANTHINE
INHALATION
METABOLISM
MUTAGENS
NITRO COMPOUNDS
POLYCYCLIC AROMATIC HYDROCARBONS
RISK ASSESSMENT
SALMONELLA
STRUCTURE-ACTIVITY RELATIONSHIPS