DECREASED ABILITY OF CELLS OVEREXPRESSING MYC PROTEINS TO REDUCE PEROXIDE AND HYDROPEROXIDES

Hydroperoxides are reduced in mammalian cells by a coupled enzyme path way involving glutathione peroxidase, glutathione reductase and the ox idative limb of the pentose cycle. Oxidation of glucose-6-phosphate by the pentose cycle yields two molecules of NADPH, which can reduce two hydroperoxide molecules to the corresponding alcohol. Rat embryo fibr oblasts (REF) transfected with v-myc reduce hydroperoxides slower than the primary REF cell line-measured both as real lime peroxide loss an d as increased glucose oxidation via the pentose cycle. The v-myc tran sfected cell line is 50-fold more sensitive to the toxic effects of tB u-OOH. The decreased reduction of peroxides by v-myc transfected cells is not due to changes in the activities of GSH reductase or the enzym es of the oxidative pentose cycle, since diamide stimulates PC activit y equally in both cell lines. In addition, the activities of these enz ymes, measured in cell homogenates do not differ significantly between the cell lines. Also total GSH peroxidase activity, assayed in cell h omogenates, is not significantly different between the cell lines. Two human tumour cell lines which overexpress myc family proteins: NCI-H6 9, a small-cell lung cancer line which expresses elevated levels of N- myc, and HL-60 cells which overexpress c-myc, also exhibit low levels of pentose cycle stimulation in the presence of tBu-OOH, and a decreas ed capacity to reduce hydrogen peroxide by peroxide electrode.