Dietary omega-3 fatty acids as potential inhibitors of carcinogenesis: effect on DNA adduct formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in mice and rats

Josyula, Shylaja; Schut, Herman A.J.

doi:10.1016/s0278-6915(99)00018-6

Cited by 14 publications

(8 citation statements)

References 57 publications

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“…Next to interference in COX‐mediated pathways, decrease in HCA‐DNA adduct formation may also be due to interactions between PUFA and cytochrome P450 enzymes. Josyula and Schut suggest that n‐3 fatty acids may affect the synthesis or catalytic activity of cytochromes P450 1A1 and 1A2 [27]. Furthermore, various studies describe the possible modulation of several cytochromes P450 by dietary fish oil, although specific effects on isoforms 1A1 and 1A2 remain unknown [52,53].…”

Section: Discussionmentioning

confidence: 99%

Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase‐mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells

Moonen

Dommels

Zwam

et al. 2004

Molecular Carcinogenesis

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Dietary heterocyclic aromatic amines (HCA) and polyunsaturated fatty acids (PUFA) are both believed to play a role in colon carcinogenesis, and are both substrate for the enzyme cyclooxygenase (COX). In HCA-7 cells, highly expressing isoform COX-2, we investigated the effects of PUFA on prostaglandin synthesis and DNA adduct formation by the HCA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Furthermore, we studied the role of COX, COX-2 in particular, and cytochrome P4501A2 (CYP1A2) by using the enzyme inhibitors indomethacin (IM), NS-398, and phenethyl isothiocyanate (PEITC), respectively. COX-mediated formation of prostaglandin E2 (PGE2) from linoleic acid (LA) showed that HCA-7 cells can convert LA into arachidonic acid (AA). Alternatively, eicosapentaenoic acid (EPA) was found to compete with AA for COX. Strongly decreased PGE2 levels by addition of IM demonstrated involvement of COX in PUFA metabolism. Both IM and NS-398 inhibited adduct formation by HCA to nearly the same extent, indicating involvement of COX-2 rather than COX-1, while CYP1A2 activity in HCA-7 cells was demonstrated by addition of PEITC. Overall, inhibiting effects were stronger for PhIP than for IQ. HCA-DNA adduct formation was stimulated by addition of PUFA, although high PUFA concentrations partly reduced this stimulating effect. Finally, similar effects for n-3 and n-6 fatty acids suggested that adduct formation may not be the crucial mechanism behind the differential effects of PUFA on colon carcinogenesis that have been described. These results show that COX, and COX-2 in particular, can play a substantial role in HCA activation, especially in extrahepatic tissues like the colon. Furthermore, the obvious interactions between PUFA and HCA in COX-2 expressing cancer cells may be important in modulating colorectal cancer risk.

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Section: Discussionmentioning

confidence: 99%

Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase‐mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells

Moonen

Dommels

Zwam

et al. 2004

Molecular Carcinogenesis

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“…2,3) Since the level of PhIP-DNA adducts in the small intestine were demonstrated to be almost equivalent to that in the colon, 17) some other unknown modifying factors may exist to generate the differential susceptibility between the small intestine and colon in mice.…”

Section: Discussionmentioning

confidence: 99%

“…It is interesting to note that the majority of intestinal tumors arose in the small intestine, not in the colon, which A B is one of the main target organs of PhIP in rats. 2,3) Since the level of PhIP-DNA adducts in the small intestine were demonstrated to be almost equivalent to that in the colon, 17) some other unknown modifying factors may exist to generate the differential susceptibility between the small intestine and colon in mice. C57BL/6N mice were also susceptible to the induction of lymphomas of B-cell origin.…”

Section: Discussionmentioning

confidence: 99%

Induction of Intestinal Tumors and Lymphomas in C57BL/6N Mice by a Food‐borne Carcinogen, 2‐Amino‐l‐methyl‐6‐phenylimidazo[4,5‐b]pyridine

Ochiai

Imai

Sügimura

et al. 2002

Japanese Journal of Cancer Research

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2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine contained in cooked meat and fish. Although PhIP has been demonstrated to induce various types of tumors in rats, lymphomas predominated in mice using the CDF1 strain. To investigate the carcinogenic activity of PhIP on other organs in mice with a different genetic background, PhIP was administered to C57BL/6N mice. After a 40-week administration of 300 ppm of PhIP in a high-fat diet followed by continuous feeding with a high fat diet, C57BL/6N mice developed adenomas and adenocarcinomas in the small intestine, the incidences being 52% in males and 68% in females at weeks 95 and 70, respectively. Lymphomas of B-cell origin also developed in both sexes as frequently as in the CDF1 strain, incidences being 48% in males and 32% in females. Although the incidence in PhIP-treated female mice did not differ from that in the control mice, lymphomas developed significantly earlier in the PhIP-treated mice. The present study demonstrated that the intestinal tract is another potential target of PhIP-induced carcinogenesis in mice, and that the carcinogenic activity of PhIP could be affected by the genetic background of the animals.

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“…10-23), 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhiP; ref. 24), and a Her-2/ transgenic mouse model (25). Some studies did not include any carcinogenic agent but simply evaluated the effect of diet on normal mammary gland biomarkers (26,27).…”

Section: Preclinical Studies Tend To Support a Protective Effect Of Nmentioning

confidence: 99%

“…Only 2 studies (4,22) verified the chemical composition of the diet. Most studies reported the composition information provided to them by their fish oil supplier (6,7,16,(24)(25)(26), which may vary, as suggested by the reported range of concentrations of individual FA expected to be present in a batch of fish oil. Such Figure 1.…”

Section: Confounding Factors That May Contribute To Variability Seen mentioning

confidence: 99%

Chemoprevention of Breast Cancer by Fish Oil in Preclinical Models: Trials and Tribulations

et al. 2011

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Despite the perception that omega-3 fatty acids (n-3 FA) protect against breast cancer, epidemiologic studies have yielded inconsistent results. Although preclinical data have been, in general, more supportive of a protective effect of n-3 FA on breast cancer, inconsistencies still remain, which preclude definite conclusions or in-depth mechanistic investigations despite 30 years of research in this area. In this review, we discuss key variables that may account for inconsistencies of results across preclinical studies and provide recommendations for future experiments testing the chemopreventive effect of n-3 FAs in breast cancer, as part of a multiagent approach under rigorously controlled conditions. Cancer Res; 71(19); 6091-6. Ó2011 AACR.

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Dietary omega-3 fatty acids as potential inhibitors of carcinogenesis: effect on DNA adduct formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in mice and rats

Cited by 14 publications

References 57 publications

Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase‐mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells

Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase‐mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells

Induction of Intestinal Tumors and Lymphomas in C57BL/6N Mice by a Food‐borne Carcinogen, 2‐Amino‐l‐methyl‐6‐phenylimidazo[4,5‐b]pyridine

Chemoprevention of Breast Cancer by Fish Oil in Preclinical Models: Trials and Tribulations

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