Th. Tseng et al., PROMOTION OF COLON CARCINOGENESIS THROUGH INCREASING LIPID-PEROXIDATION INDUCED IN RATS BY A HIGH CHOLESTEROL DIET, Cancer letters, 100(1-2), 1996, pp. 81-87
To examine the influence of hypercholesteremia on 1,2-dimethylhydrazin
e (DMH)-induced rat colon cancer, Sprague-Dawley rats received dietary
cholesterol (CH, 0-2%) and cholic acid (CA, 0.25%) with or without DM
H (20 mg/kg, s.c. injection) for 18 weeks. The rats receiving dietary
cholesterol and cholic acid all significantly increased total serum ch
olesterol and lipids but only a high cholesterol diet (2% CH plus 0.25
% CA) decreased the activity of glutathione peroxidase (GSH-Px) and in
creased the formation of peroxides in the colon (P < 0.01). The rats t
hat received the combination of DMH and high cholesterol diet enhanced
these effects. At the end of the experiment, the diet group administe
red DMH and high cholesterol (2% CH plus 0.25% CA) developed colon ade
noma at 50% of incidence in pathological examination, but no colon ade
noma formed in the rats treated with high cholesterol alone. It is sup
posed that a non-carcinogenic agent like cholesterol may potentiate th
e carcinogenicity of DMH in rats via an increase of lipid peroxidation
and decrease in the activity of peroxidase in the target organ.