Oxidative stress in tumour-bearing fore-stomach and distant normal organs of Swiss albino mice.
Antioxidant status in the tumour-bearing fore-stomach and distant normal organs (liver, spleen, kidney and heart) was investigated in Swiss albino mice. In addition, the cytochrome P450 (cyt P450) system was also examined in the liver. Benzo(a)pyrene [B(a)P] (8 doses of 1 mg/0.1 ml) was administered twice a week for 4 weeks to develop fore-stomach tumour. The animals were sacrificed at the end of 140 days. The specific activities of catalase (CAT), DT-diaphorase (DTD) and glutathione-S-transferase (GST) were found decreased, and the level of reduced glutathione (GSH) and the specific activity of lactate dehydrogenase (LDH) increased in the tumour-bearing fore-stomach; however, no change was observed in superoxide dismutase (SOD) activity. The specific activities of antioxidant enzymes, and levels of GSH were also altered in the normal organs, depending upon the type of tissue. In addition, the contents of cyt P450 and cyt b5, and the activity of NADPH cyt P450 reductase were significantly decreased in the liver. The results suggest increased oxidative stress in the tumour, and disturbance in the cooperative antioxidant functions in the distant normal organs. Inhibition of cyt P450 system reflected the possible adverse effect on drug metabolism function of the liver. Since, the antioxidant potential and the drug metabolism function were altered, the findings may have relevance to the radiation and chemotherapy of cancer.
Radiation and Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Gagandeep
A R
AR
Rao
R K
RK
Kale
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001564:Benzo(a)pyrene / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000502:physiology; D008658:Inactivation, Metabolic; D007668:Kidney / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D018384:Oxidative Stress; D013154:Spleen / Q000378:metabolism; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*
D000975:Antioxidants; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D007770:L-Lactate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D005978:Glutathione