Pharmacogenetics of cyclic guanylate, antioxidants, and antioxidant enzymes in Saccharomyces

Supplements of antioxidants, superoxide dismutase (SOD), catalase, cyclic guanylate (cGMP), and theophylline, or omission of iron and copper from the medium are therapeutic for the inferior growth and viability of yeast mutants doubly deficient in mitochondrial and exocellular SOD isozymes under oxidative stresses. Cyclic adenylate tends to be ineffective or counterproductive. Oxy-stress resistant revertants are cross-resistant to other oxy-stresses and acquire one, the other, or both isozymes. The principal conclusions are: i) a genetic defect in cGMP metabolism probably compromises regulation of the enzymes' synthesis; ii) the enzymes are only essential for growth and viability under oxidative stresses; iii) oxidative toxicity is mediated by both exo- and endocellular oxy-radicals, particularly hydroxyl radicals; and iv) the pharmacogenetic features and the mutants' phenotypes are quite similar to those of negative antioxidant enzyme regulatory mutants of the related ascomycete Neurospora.