Suppression of azoxymethane-induced rat colon carcinoma development by a fish oil component, docosahexaenoic acid (DHA)

Abstract

The effects of intragastric gavage administration of docosahexaenoic acid (DNA) , a major component of fish oil, on azoxymethane (AOM)-induced colon carcinogenesis in rats was investigated. Male F344 rats were treated with 15 mg/kg body wt of AOM once a week, for two weeks. The animals were given either 1 ml of DHA or water intragastrically 5 times a week, starting the day before the first carcinogen treatment. The numbers of AOM-induced aberrant crypt foci in the rats given DHA were 76% and 62% of the control values, at 4 and 12 weeks, respectively. After 36 weeks of DHA treatment, colon tumors were counted and examined histologically. The blood plasma levels of prostaglandin E2 (PGE2) and polyunsaturated fatty acids were also quantified. The incidences of colon cancer did not differ, being 96% and 92% in the AOM and AOM+DHA groups, respectively. Colon cancer multiplicity was, however, significantly decreased by the DHA treatment; 3.65 +/- 2.18 in the AOM group and 2.41 +/- 1.58 in the AOM+DHA group (P <0.01). Notably, the numbers of moderately differentiated adenocarcinomas in the middle and distal colon in the DHA-treated group were lower than in the AOM group. The levels of PGE2 and arachidonic acid in the blood plasma of DHA-treated rats were also significantly lower than in the AOM group. These results suggest that DHA exerts its inhibitory effect on colon carcinogenesis by modulating lipid metabolism and inhibiting the arachidonic cascade.

Characterization of Dysplastic Aberrant Crypt Foci in the Rat Colon Induced by 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine

“…24 In rat models, although hundreds of ACF are induced per animal by azoxymethane (AOM), and K-ras mutations are frequently observed in those ACF, only a few colon tumors are observed per animal. [25][26][27] Moreover, some compounds that effectively suppress the induction of ACF by AOM in rats, eg, 2-(carboxyphenyl) retinamide or genistein, enhance the development of colon cancers. 23,28,29 This discrepancy could be caused by the heterogeneous nature of ACF and also by a wide range of biological consequences of ACF.…”

Meat and cancer: meat as a component of a healthy diet

“…mice showed resistance to AOM induction of neoplastic colon lesions (Watanabe et al, 1999). o3 fatty acids (linolenic acid) however, suppress colon carcinogenesis by inhibiting the arachidonic pathway (Takahashi et al, 1997).…”

Study on Synthesis, Characterization and Antiproliferative Activity of Novel Diisopropylphenyl Esters of Selected Fatty Acids

“…The common approach to overcome such difficulty and to increase the drug efficiency is to use the anticancer drug conjugated with other substitute. Hence, a molecule that shows suitable properties is chemically changed by coupling to another therapeutically active compound to achieve the best combination of properties in forming the most effective anticancer drug 3,4 . Among these chemically modified drugs are the esters of fatty acids, chosen as anticancer drug conjugates because of their low toxicity 5,6 .…”