Promotion of colon carcinogenesis through increasing lipid peroxidation induced in rats by a high cholesterol diet.
To examine the influence of hypercholesteremia on 1,2-dimethylhydrazine (DMH)-induced rat colon cancer, Sprague-Dawley rats received dietary cholesterol (CH, 0-2%) and cholic acid (CA, 0.25%) with or without DMH (20 mg/kg, s.c. injection) for 18 weeks. The rats receiving dietary cholesterol and cholic acid all significantly increased total serum cholesterol and lipids but only a high cholesterol diet (2% CH plus 0.25% CA) decreased the activity of glutathione peroxidase (GSH-Px) and increased the formation of peroxides in the colon (P < 0.01). The rats that received the combination of DMH and high cholesterol diet enhanced these effects. At the end of the experiment, the diet group administered DMH and high cholesterol (2% CH plus 0.25% CA) developed colon adenoma at 50% of incidence in pathological examination, but no colon adenoma formed in the rats treated with high cholesterol alone. It is supposed that a non-carcinogenic agent like cholesterol may potentiate the carcinogenicity of DMH in rats via an increase of lipid peroxidation and decrease in the activity of peroxidase in the target organ.
Tseng
T H
TH
Institute of Biochemistry, Chung Shan Medical and Dental College, Taiwan, ROC.
Hsu
J D
JD
Chu
C Y
CY
Wang
C J
CJ
D019813:1,2-Dimethylhydrazine; D000230:Adenocarcinoma / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000009:adverse effects* / Q000378:metabolism; D019826:Cholic Acid; D002793:Cholic Acids / Q000633:toxicity; D003043:Cocarcinogenesis; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D003864:Depression, Chemical; D004127:Dimethylhydrazines / Q000633:toxicity; D005979:Glutathione Peroxidase / Q000378:metabolism; D006937:Hypercholesterolemia / Q000209:etiology / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008297:Male; D010545:Peroxides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D002791:Cholesterol, Dietary; D002793:Cholic Acids; D004127:Dimethylhydrazines; D008055:Lipids; D010545:Peroxides; D002784:Cholesterol; D005979:Glutathione Peroxidase; D019826:Cholic Acid; D019813:1,2-Dimethylhydrazine