Modification of microsomal metabolism of benzo(a)pyrene (BaP) by superoxide generated in vitro

Conference · Sat Mar 01 00:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5073205

Byczkowski, J Z; Gessner, T

Reactive oxygen species may play a role in bioactivation of BaP and its procarcinogenic metabolites. The effect of superoxide (O/sub 2/) and/or other active oxygen species, generated in vitro by xanthine/xanthine oxidase (X/XO) +/- Fe/sup 3 +/, on BaP metabolism by mouse liver microsomes fortified with NADPH and UDP-glucuronic acid was examined. Analysis of the reaction mixtures by reversed-phase high pressure liquid chromatography in methanol-water gradient showed that the peroxidative conditions evoked by X/XO + Fe/sup 3 +/ decreased the overall metabolism of /sup 14/C-BaP by some 40% and decreased glucuronidation of BaP metabolites by about 85%, while protein bound metabolites increased by 80%. Even without added Fe/sup 3 +/, O/sub 2/ increased the production of epoxides by 174%. Addition of superoxide dismutase reversed the decreases in both glucuronidation and overall metabolism of BaP. This indicates that O/sub 2/ switches the BaP metabolism to direct epoxidation and increases the amount of intermediates able to bind protein, while damage to membrane bound enzymes curtails further metabolism of BaP. Thus, it appears that during oxidative burst, such as in inflammatory reactions, there would be a limited mixed function oxidase mediated bioactivation of BaP.

• Research Organization: Roswell Park Memorial Institute, Buffalo, NY
• OSTI ID: 5073205
• Report Number(s): CONF-8604222-; TRN: 86-036906
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BENZOPYRENE
METABOLISM
SUPEROXIDE RADICALS
BIOLOGICAL EFFECTS
CARBON 14 COMPOUNDS
EPOXIDES
GLUCURONIC ACID
IN VITRO
IRON
LIQUID COLUMN CHROMATOGRAPHY
LIVER
METABOLITES
MICE
MICROSOMES
NADP
OXIDOREDUCTASES
TRACER TECHNIQUES
ALDEHYDES
ANIMALS
AROMATICS
BODY
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHROMATOGRAPHY
COENZYMES
CONDENSED AROMATICS
DIGESTIVE SYSTEM
ELEMENTS
ENZYMES
GLANDS
HYDROCARBONS
HYDROXY ACIDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
METALS
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
ORGANS
RADICALS
RODENTS
SEPARATION PROCESSES
TRANSITION ELEMENTS
VERTEBRATES
550501* - Metabolism- Tracer Techniques