Role of glutathione in the induction of apoptosis and c-fos and c-jun mRNAs by oxidative stress in tumor cells.
We have used two tumor cell clones (B9 and G2), derived from the methylcholanthrene-induced murine fibrosarcoma GR9 and normal BALB/c3T3 fibroblasts, to study the ability of t-BOOH derived reactive oxygen radicals to induce oxidative stress, apoptosis and c-fos and c-jun mRNA transcription. These clones differ in terms of their major histocompatibility complex (MHC) (H-2) class I genes expression, their tumor induction and metastatic potential and their reduced glutathione (GSH) levels. Incubation of both cell clones in the presence of t-BOOH results in the increase of 8-oxo-2'-deoxyguanosine (8-oxo-dG) and malondialdehyde and the decrease of GSH. The xenobiotic also induces the transcription of c-fos and c-jun mRNAs in normal fibroblasts and in B9 cell clone but not in G2 cell clone. In addition, G2 cell clone is more resistant to apoptosis when compared with normal fibroblasts or B9 cell clone. Higher levels of GSH in G2 cell clone may be the reason of their lower transactivation response and apoptosis. Thus lowering GSH concentration may be convenient not only for the efficiency of chemotherapy but also to induce a rather fast and direct apoptosis mechanisms in tumor cells. Most commonly antioxidants tested, superoxide dismutase, catalase, GSH and thiourea, were effective in the inhibition of t-BOOH-induced c-fos and c-jun mRNA transcription in normal fibroblasts suggesting, as expected, that different oxygen species are involved in the observed effects induced by the xenobiotic.
Tormos
Carmen
C
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universitat de Valencia, Avda. Blasco Ibañez 17, 46010 Valencia, Spain.
Javier Chaves
F
F
Garcia
Maria José
MJ
Garrido
Federico
F
Jover
Ramiro
R
O'Connor
José Enrique
JE
Iradi
Antonio
A
Oltra
Ana
A
Oliva
Maria R
MR
Sáez
Guillermo T
GT
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D041702:BALB 3T3 Cells; D017931:DNA Primers / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005354:Fibrosarcoma / Q000139:chemically induced / Q000378:metabolism / Q000556:secondary; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D000975:Antioxidants; D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D020122:tert-Butylhydroperoxide; D003849:Deoxyguanosine; D005978:Glutathione