V79 Chinese hamster cells have previously been shown to lack the capacity to detoxify the mutagenic and carcinogenic compound (+)-anti-benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide [(+)-anti-BPDE] by Pi class glutathione transferase (GSTPi)-catalysed conjugation with GSH, although these cells contain such an enzyme [Romert, Dock, Jenssen and Jernström (1989) Carcinogenesis 10, 1701–1707; Swedmark, Romert, Morgenstern and Jenssen (1992) Carcinogenesis 13, 1719–1723; Swedmark and Jenssen (1994) Gene 139, 251–256]. Previous findings also indicate that these results do not depend on an inactive GSTPi 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 selectively [Swedmark, Jernström and Jenssen (1996) Biochem. J. 318, 533–538]. The present 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 cell extract present and that the factor(s) is heat-resistant and has a molecular mass of less than 10 kDa, suggesting that the factor(s) is (are) non-proteinaceous in nature.
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Research Article|
July 25 2000
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
Kathrin SUNDBERG;
Kathrin SUNDBERG
*National Institute of Environmental Medicine, Karolinska Institutet, S-171 77 Stockholm, Sweden
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Bengt JERNSTRÖM;
Bengt JERNSTRÖM
*National Institute of Environmental Medicine, Karolinska Institutet, S-171 77 Stockholm, Sweden
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Stellan SWEDMARK
Stellan SWEDMARK
1
†Department of DMPK Discovery, R&D Södertälje, AstraZeneca, S-151 85 Södertälje, Sweden
1To whom correspondence should be addressed (e-mail Stellan.Swedmark@astrazeneca.com).
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Publisher: Portland Press Ltd
Received:
May 15 2000
Accepted:
May 26 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2000
2000
Biochem J (2000) 349 (3): 693–696.
Article history
Received:
May 15 2000
Accepted:
May 26 2000
Citation
Kathrin SUNDBERG, Bengt JERNSTRÖM, Stellan SWEDMARK; 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 1 August 2000; 349 (3): 693–696. doi: https://doi.org/10.1042/bj3490693
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