Human glutathione S-transferase M1 null genotype is associated with a high inducibility of cytochrome P450 1A1 gene transcription.
We investigated the transcriptional regulation of cytochrome P450 1A1 (CYP1A1) gene in human lymphoblastoid B cells and report that a high inducibility of CYP1A1 gene transcription by 2,3,7,8-tetrachlorodibenzo-p-dioxin is associated with glutathione S-transferase M1 (GSTM1) null genotype, whereas the presence of at least one GSTM1 allele is correlated with induction of only low levels of CYP1A1 mRNA by 2,3,7,8-tetrachlorodibenzo-p-dioxin. These data underline the major importance of the CYP1A1 inducibility phenotype associated with the homozygous GSTM1 null genotype in chemically induced cancers.
Vaury
C
C
Institut Jacques Monod, Centre National de la Recherche Scientifique, Paris, France.
Lainé
R
R
Noguiez
P
P
de Coppet
P
P
Jaulin
C
C
Praz
F
F
Pompon
D
D
Amor-Guéret
M
M
D001483:Base Sequence; D002461:Cell Line, Transformed; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000201:enzymology; D008969:Molecular Sequence Data; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D000072317:Polychlorinated Dibenzodioxins; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase