DNA adducts and carcinogenicity of nitro-polycyclic aromatic hydrocarbons

Journal Article · Sat Oct 01 00:00:00 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-; ISSN 0091-6765; TRN: 97:002101-0006
• Journal Information: Environmental Health Perspectives, Vol. 102, Issue Suppl.6; Conference: 5. international conference on carcinogenic and mutagenic n-substituted aryl compounds, Wursburg (Germany), 18-21 Oct 1992; Other Information: PBD: Oct 1994
• Country of Publication: United States
• Language: English

Related Subjects

02 PETROLEUM
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
55 BIOLOGY AND MEDICINE
BASIC STUDIES
CONDENSED AROMATICS
BIOLOGICAL EFFECTS
NITRO COMPOUNDS
EXHAUST GASES
RISK ASSESSMENT
DIESEL FUELS
COMBUSTION PRODUCTS
INHALATION
DNA ADDUCTS
HYPOXANTHINE
METABOLISM
MUTAGENS
POLYCYCLIC AROMATIC HYDROCARBONS
SALMONELLA
STRUCTURE-ACTIVITY RELATIONSHIPS