IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

NAPHTHALENE 397
Table 8. Species comparison in the rates of conversion of naphthalene to
naphthalene 1,2-oxides by recombinant enzymes
Recombinant
enzyme
Species Rate of
metabolism a
CYP2F1 Human 35.5 c
CYP2F2 Mouse d
104 000 e
Stereoselectivity b
Modified from Buckpitt et al. (2002)
a Expressed in pmol/min/nmol enzyme
b Expressed as ratio of epoxide stereoisomers (1R,2S):(1S,2R)
c Total amount of glutathione conjugates (1 + 2 + 3) (see Figure 2)
d Sequence homology with human enzyme, 82%
e Amount of glutathione conjugate 2 (see Figure 2)
Reference
0.13:1 Lanza et al. (1999)
66:1 Shultz et al. (1999)
Figure 2. Metabolism of naphthalene by murine CYP2F2 to reactive epoxides and
their subsequent trapping as glutathione conjugates
From Shultz et al. (1999)
Conjugates are numbered in the order of their elution after separation by reversed-phase HPLC.
GSH Tx, glutathione transferases
P450m50b [CYP2F2], which formed predominantly naphthalene 1R,2S-oxide (see
Table 8 and Figure 2). Ritter et al. (1991) confirmed that the primary isoform responsible
for naphthalene metabolism in the mouse lung was in the 2F subfamily. It was not inducible
by phenobarbital, pyrazole, pregnenolone 16α-carbonitrile or 3-methylcholanthrene.
Kanekal et al. (1991) examined the relationship between cytotoxicity and metabolism
of naphthalene oxide using the isolated perfused lung of male CFW mice.