sup 32 P analysis of DNA adducts in tissues of benzene-treated rats

Journal Article · Sat Jul 01 04:00:00 EDT 1989 · Environmental Health Perspectives; (USA)

DOI:https://doi.org/10.2307/3430783· OSTI ID:5181946

Reddy, M V; Blackburn, G R; Schreiner, C A; Mehlman, M A; Mackerer, C R ^[1]

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1. Mobil Oil Corp., Princeton, NJ (USA)

Solid tumors have been reported in the Zymbal gland, oral and nasal cavities, liver, and mammary gland of Sprague-Dawley rats following chronic, high-dose administration of benzene. The carcinogenic activity of benzene is thought to be caused by activation to toxic metabolites that can interact with DNA, forming covalent adducts. A nuclease P1-enhanced 32P-postlabeling assay, having a sensitivity limit of 1 adduct in 10(9-10) DNA nucleotides, was found suitable for measuring aromatic DNA adducts derived in vitro from catechol, benzenetriol (BT), phenol, hydroquinone (HQ), and benzoquinone (BQ), potential metabolites of benzene. When DNA specimens isolated from tissues of female Sprague-Dawley rats at 24 hr after an oral gavage dose of 200 to 500 mg/kg, 5 days/week, in olive oil (3 mL/kg) for 1 day, 1 week, 5 weeks, and 10 weeks were analyzed by the 32P-postlabeling procedure, no aromatic adducts were detected unequivocally with DNA samples of liver, kidney, bone marrow, and mammary gland. With Zymbal gland DNA, three weak spots at levels totaling four lesions per 10(9) DNA nucleotides were seen only after 10 weeks of treatment, and these adducts did not correspond chromatographically to major adducts in vitro from the above specified compounds. Consequently, this finding requires confirmatory experiments. This distinct adduct pattern may relate to tumor induction in this organ following benzene administration. Our results also indicate that DNA adducts derived from catechol, BT, phenol, HQ, and BQ are either not formed in vivo with benzene or formed at levels below the detection limit of 1 adduct per 10(9-10) DNA nucleotides.

• OSTI ID: 5181946
• Journal Information: Environmental Health Perspectives; (USA), Journal Name: Environmental Health Perspectives; (USA) Vol. 82; ISSN 0091-6765; ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ANIMALS
AROMATICS
AUTORADIOGRAPHY
BENZENE
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
BODY AREAS
CARCINOGENESIS
CHRONIC EXPOSURE
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DNA ADDUCTS
FACE
GLANDS
HEAD
HYDROCARBONS
ISOTOPES
LIGHT NUCLEI
LIVER
MAMMALS
MAMMARY GLANDS
METABOLIC ACTIVATION
METABOLITES
NOSE
NUCLEI
ODD-ODD NUCLEI
ORAL CAVITY
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
RADIOISOTOPES
RATS
RESPIRATORY SYSTEM
RODENTS
VERTEBRATES