Correlation between production of benzo(A)pyrene metabolites and BPDE I-DG adduct levels in human epithelial cells in vitro pretreated with cytochrome P450 inhibitors or inducer

Conference · Fri May 01 00:00:00 EDT 1987 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6365861

Lehman, T A; Milo, G E

Human epidermal keratinocytes were established from neonatal foreskins. Cultures were pretreated for 24 hr with either butylated hydroxyanisole (BHA), methyl butylated hydroxyanisole (MeBHA) or 7,8 benzoflavone (7,8BF). For metabolite detection studies, cultures were treated with radiolabeled benzo(a)pyrene (BP) for 24 hr. Ethyl acetate soluble metabolites were extracted for HPLC analysis. BHA and 7,8BF pretreatment both significantly decreased intracellular production of 7,8 diol BP compared to cultures treated only with radiolabeled BP. MeBHA pretreatment greatly increased intracellular 7,8 diol BP formation compared to BP treated controls. For DNA adduct analysis, cultures were pretreated as described above, and then treated for 24 hr with non-radiolabeled BP. Cellular DNA was isolated and /sup 32/P-postlabeled for adduct analysis. Cultures pretreated with either BHA or 7,8BF formed significantly fewer BPDE I-dG adducts than nonpretreated cultures, while cultures pretreated with MeBHa formed more BPDE I-dG adducts. Thus, BHA and 7,8BF act similarly in reducing BP activation and adduct formation while MeBHa, a structural analog of BHA, increases BP activation and adduct formation in human keratinocyte cultures in vitro.

• Research Organization: Ohio State Univ., Columbus
• OSTI ID: 6365861
• Report Number(s): CONF-870644-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 46:6; Conference: 78. annual meeting of the American Society of Biological Chemists conference, Philadelphia, PA, USA, 7 Jun 1987
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
ANISOLE
GENETIC EFFECTS
METABOLISM
BENZOPYRENE
FLAVONES
ANIMAL CELLS
DNA
DNA ADDUCTS
ENZYME INHIBITORS
EPITHELIUM
IN VITRO
LIQUID COLUMN CHROMATOGRAPHY
MAN
METABOLITES
PHOSPHORUS 32
TRACER TECHNIQUES
ADDUCTS
ANIMAL TISSUES
ANIMALS
AROMATICS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
CHROMATOGRAPHY
CONDENSED AROMATICS
DAYS LIVING RADIOISOTOPES
ETHERS
FLAVENOIDS
HYDROCARBONS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PHOSPHORUS ISOTOPES
PRIMATES
RADIOISOTOPES
SEPARATION PROCESSES
TISSUES
VERTEBRATES
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