Many solid tumors contain substantial fractions of hypoxic cells which are relatively resistant to both radiation therapy and certain cytotoxic drugs. We have previously shown that exposure of human HT29 cells to hypoxic conditions results in the overexpression of certain enzymes involved in the detoxication of xenobiotics, including NAD(P)H:(quinone acceptor) oxidoreductase (DT)-diaphorase, an...

Peroxisome proliferators (PPs) cause hepatomegaly, peroxisome proliferation, and hepatocarcinogenesis in rats and mice, whereas hamsters are less responsive to PPs. PPs increase the activities of enzymes involved in peroxisomal beta-oxidation and omega-hydroxylation of fatty acids, which has been hypothesized to result in oxidative stress. The hypothesis of this study was that differential modu...

Hereditary methemoglobinemia has been found to have a relatively high prevalence in Alaskan Eskimos and Indians (1). Persons with this condition have been found to have a complete lack of diphosphopyridine nucleotide diaphorase activity in red cells (2). Of the 21 known cases of methemoglobinemia in 13 families in Alaska, 12 cases in 7 families occurred in Ingalik Indians, a small group of abou...

NADH-diaphorase, one of flavoenzymes, is known to lose scarcely its activity in riboflavin deficiency. In that case, as reported previously (1), the enzyme still has its activity even in the intestinal mucosa, a very actively regenerating tissue. We therefore assumed that this enzyme increased its activity directly before mitosis. In order to confirm this assumption we have studied the activity...

It has already been reported that muscle necrosis induced by various phenylenediamine derivatives are correlated with their autoxidation rate. Now in a more detailed investigation of the cytotoxic mechanism using a model system of isolated hepatocytes and ring-methylated structural isomer durenediamine (DD) we have shown that under aerobic conditions, phenylenediamine induced cytotoxicity and R...

It has already been reported that muscle necrosis induced by various phenylenediamine derivatives are correlated with their autoxidation rate. Now in a more detailed investigation of the cytotoxic mechanism using a model system of isolated hepatocytes and ring-methylated structural isomer durenediamine (DD) we have shown that under aerobic conditions, phenylenediamine induced cytotoxicity and R...