S. Tuttle et al., DECREASED ABILITY OF CELLS OVEREXPRESSING MYC PROTEINS TO REDUCE PEROXIDE AND HYDROPEROXIDES, British Journal of Cancer, 74, 1996, pp. 140-144
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.