Reduced benzo-a-pyrene activation potential in lymphocytes from chronic alcoholics.
The effect of chronic ethanol consumption on the cellular metabolism of benzo-a-pyrene (BaP) is investigated in human peripheral lymphocytes obtained from 6 proven alcoholic addicts and 5 healthy donors. Lymphocytes convert BaP to dihydrodiols, diol-epoxides, phenols, quinone derivatives and polyhydroxylated forms. Sulfate, glucuronide and glutathione conjugates are also detected. The average production of metabolites is much lower in lymphocytes of alcoholics and a net global decrease of "active" metabolite production, i.e., diols and BPDE, is also observed. In contrast, conjugated metabolites are formed in increased amounts. The data indicate that the metabolism of BaP in lymphocytes from chronic alcoholics is characterized essentially by a lowered rate of metabolized BaP and a reduction of their BaP activation potential, as seen by the increased production of conjugated metabolites and the markedly decreased protein-bound active mutagen.
Schmitt
M
M
INSERM U-184, Institut de Chimie Biologique, Faculté de Médecine 11, Strasbourg, France.
Doffoel
M
M
Diebold-Simoni
P
P
Toussaint
J L
JL
Kempf
J
J
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000378:metabolism*; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001711:Biotransformation; D002463:Cell Membrane Permeability; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D003577:Cytochrome P-450 Enzyme System