Exposure to benzene was recently reported to lower the cytochrome P450 (CYP
) content in phenobarbital-pretreated rats in vivo (Gut et al., Environ. He
alth Perspect. 104 (1996) 1211-1218). This study followed the ability of qu
inonic benzene metabolites (catechol, hydroquinone, and benzoquinone) to de
stroy CYP in liver microsomes from rats pretreated with various inducers an
d in human liver microsomes. Sensitivity of CYP isoforms to destruction was
revealed and the interspecies differences assessed. The spectrophotometric
evaluations of the total CYP content, assay of CYP marker activities, and
electrophoresis with immunoblotting after incubation of microsomes with qui
nones revealed that: (1) rat liver CYP activities markedly differed in sens
itivity to quinone-mediated destruction in vitro, CYP 1A and 3A being the m
ost sensitive isoforms; (2) differences in OH radicals formation and lipid
peroxidation among microsomes from rats pretreated with various CYP inducer
s were also observed; (3) semiquinone radical formation, OH radical product
ion, and induction of lipid peroxidation did not contribute significantly t
o CYP destruction by quinones; (4) the main mechanism of CYP destruction is
covalent binding of the oxidized quinone form to protein and heme moieties
of CYP; (5) quinones, mainly benzoquinone, destroy human CYP isoforms to a
much greater extent than rat enzymes and thus humans may be much more susc
eptible to the deleterious effect of benzene metabolism. In conclusion, it
is suggested that CYP destruction may be another consequence of benzene exp
osure and should be taken into consideration when evaluations of possible h
ealth risks are performed. (C) 1999 Elsevier Science Ireland Ltd. All right
s reserved.