Cellular responses to oxidative stress: the [Ah] gene battery as a paradigm.
A major source of oxidative stress in animals is plant stress metabolites, also termed phytoalexins. The aromatic hydrocarbon-responsive [Ah] gene battery is considered here as a model system in which we can study metabolically coordinated enzymes that respond to phytoalexin-induced oxidative stress. In the mouse, the [Ah] battery comprises at least six genes: two Phase I genes, CYP1A1 and CYP1A2; and four Phase II genes, Nmo-1, Aldh-1, Ugt-1, and Gt-1. All six genes appear to be regulated positively by inducers such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other ligands of the Ah receptor. In the absence of foreign inducer, the control of Nmo-1 gene expression is independent of the control of CYP1A1 and CYP1A2 gene expression. The radiation deletion homozygote c14CoS/c14CoS mouse is lacking about 1.1 centiMorgans of chromosome 7. Although having no detectable CYP1A1 or CYP1A2 activation, the untreated c14CoS/c14CoS mouse exhibits markedly elevated transcripts of the Nmo-1 gene and three growth arrest- and DNA damage-inducible (gadd) genes. These data suggest that the missing region on chromosome 7 in the c14CoS/c14CoS mouse contains a gene(s), which we propose to call Nmo-1n, encoding a trans-acting factor(s) that is a negative effector of the Nmo-1 and gadd genes. The three other [Ah] battery Phase II genes behave similarly to Nmo-1 in the c14CoS/c14CoS mouse. This coordinated response to oxidative stress and DNA damage, by way of the release of a mammalian battery of genes from negative control, bears an interesting resemblance to the SOS response in bacteria.
Nebert
D W
DW
Laboratory of Developmental Pharmacology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Petersen
D D
DD
Fornace
A J
AJ
D000818:Animals; D002273:Carcinogens; D004249:DNA Damage / Q000235:genetics; D005796:Genes; D010084:Oxidation-Reduction; D010936:Plant Extracts / Q000633:toxicity*; D011809:Quinones / Q000633:toxicity; D012717:Sesquiterpenes; D013312:Stress, Physiological / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D013729:Terpenes; D000094162:Phytoalexins
D002273:Carcinogens; D010936:Plant Extracts; D011809:Quinones; D012717:Sesquiterpenes; D013729:Terpenes; D000094162:Phytoalexins