Glutathione conjugation protects some, but not all, cell lines against DNA binding of benzo[alpha]pyrene metabolites.
Three major types of cell lines were distinguished according to their capacity for glutathione (GSH) conjugation of extracellularly generated benzo[alpha]pyrene (BaP) metabolites, and the level of DNA binding of such metabolites. (i) Cells, e.g. HepG2, which conjugate BaP metabolites only very poorly with GSH and are highly susceptible to DNA binding. The number of DNA adducts in these cells (approximately 10 pmol/mg DNA) is taken to be the maximum DNA binding in 'unprotected' cells. (ii) Cells, e.g. V79 and NCI-H322, which efficiently conjugate BaP metabolites with GSH but, like HepG2 cells, are 'unprotected' as indicted by maximum DNA binding. (iii) Cells, e.g. 2sFou and H4IIEC3/G-, which are positive for GSH conjugation and exhibit only very little DNA binding. When GSH conjugation in these apparently 'protected' cells is suppressed by depletion of GSH, the level of DNA binding increases to that found in 'unprotected' lines. GSH depletion does not substantially affect DNA binding in 'unprotected' cells. The results show that, although GSH conjugation is capable of suppressing DNA binding of reactive BaP metabolites in some cell types, it fails to protect against DNA binding in others. It is possible that the reactive species are compartmentalized and certain cell types are protected, because they are able to specifically trap those BaP metabolites which bind to DNA.
Hesse
S
S
GSF-Institute of Toxicology, Neuherberg/München, FRG.
Cumpelik
O
O
Mezger
M
M
Kiefer
F
F
Wiebel
F J
FJ
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D051381:Rats; D014407:Tumor Cells, Cultured / Q000378:metabolism
D001564:Benzo(a)pyrene; D004247:DNA; D005978:Glutathione