Studies on the differential inhibition of glutathione conjugate formation of (+)-anti-benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide and 1-chloro-2,4-dinitrobenzene in V79 Chinese hamster cells
K. Sundberg et al., Studies on the differential inhibition of glutathione conjugate formation of (+)-anti-benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide and 1-chloro-2,4-dinitrobenzene in V79 Chinese hamster cells, BIOCHEM J, 349, 2000, pp. 693-696
V79 Chinese hamster cells have previously been shown to lack the capacity t
o detoxify the mutagenic and carcinogenic compound (+)-anti-benzo[a]pyrene
7,8-dihydrodiol 9,10-epoxide [(+)-anti-BPDE] by Pi class glutathione transf
erase (GSTPi)-catalysed conjugation with GSH, although these cells contain
such an enzyme [Romert, Dock, Jenssen and Jernstrom (1989) Carcinogenesis 1
0, 1701-1707; Swedmark, Romert, Morgenstern and Jenssen (1992) Carcinogenes
is 13, 1719-1723; Swedmark and Jenssen (1994) Gene 139, 251-256]. Previous
findings also indicate that these results do not depend on an inactive GSTP
i enzyme, since V79 cells conjugate 1-chloro-2,4-dinitrobenzene (CDNB) with
GSH, but more likely on (a) factor(s) that inhibit(s) V79 GSTPi selectivel
y [Swedmark, Jernstrom and Jenssen (1996) Biochem. J. 318, 533-538]. The pr
esent study demonstrates that both human and V79 recombinant GSTPi enzymes
are inhibited with respect to conjugating(+)-anti-BPDE, but not CDNB, after
pre-incubation with V79-cell extract, but not with MCF-7-cell extract. In
addition, it was found that the inhibition is dependent on the amount of ce
ll extract present and that the factor(s) is heat-resistant and has a molec
ular mass of less than 10 kDa, suggesting that the factor(s) is (are) non-p
roteinaceous in nature.