Effects of D,L-2-difluoromethylornithine and indomethacin on mammary tumor promotion in rats fed high n-3 and/or n-6 fat diets

S. H. Abou-El-Ala, K. W. Prasse, R. L. Farrell, Richard Carroll, A. E. Wade, O. R. Bunce

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Virgin female Sprague-Dawley rats (50 days of age) were administered a single intragastric 10-mg dose of 7,12-dimethylbenz(a)anthracene (DMBA). Twenty-one days later they were placed on diets containing either 20% corn oil (CO), 15% menhaden oil plus 5% corn oil (MO + CO), 20% CO plus 0.5% w/w of the irreversible ornithine decarboxylase inhibitor, D,L-2-difluoromethylornithine (CO + DFMO), 20% CO plus 0.004% w/w of the cyclooxygenase inhibitor indomethacin (CO + INDO), 20% CO + 0.004% INDO + 0.5% DFMO (CO + INDO + DFMO), or 15% MO + 5% CO + 0.5% DFMO (MO + CO + DFMO). The incidence of DMBA-induced mammary tumors was significantly reduced in rats fed diets containing DFMO but not in rats fed the diet containing indomethacin. Incidences of mammary tumors at 16 weeks post-DMBA were 86% in rats fed the CO diet, 83% in rats ingesting the diet containing CO + INDO, 28% in rats fed CO + DFMO, 32% in rats fed diet containing CO + INDO + DFMO, 59% in rats fed the MO + CO diet, and 24% in rats fed the MO + CO + DFMO diet. The average number of tumors and tumor burden per tumor-bearing rat were reduced and tumor latency was increased in all rats fed diets containing DFMO. Body weight gain, but not food intake, of rats fed the 20% fat + 0.5% DFMO diets was significantly less than in rats fed the 20% fat diets. Prostaglandin E and leukotriene (LTB4) syntheses, ODC activity and mammary tumorigenesis were significantly inhibited by feeding the diet containing menhaden oil or by adding 0.5% DFMO to any of the high fat diets. Feeding a 20% CO diet containing 0.004% INDO significantly reduced prostaglandin synthesis and ODC activity and increased LTB4 synthesis of mammary tumors but did not inhibit mammary tumorigenesis. This study suggests that the 5-lipoxygenase product LTB4 may be involved in mammary tumor production. Whereas a decrease in LTB4 appears to be associated with a decrease in tumorigenesis, an increase (as seen in the indomethacin group) was not associated with any change in the tumorigenic response.

Original languageEnglish (US)
Pages (from-to)1434-1440
Number of pages7
JournalCancer Research
Volume49
Issue number6
StatePublished - 1989

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Eflornithine
Corn Oil
Indomethacin
Fats
Breast Neoplasms
Diet
Leukotriene B4
9,10-Dimethyl-1,2-benzanthracene
Carcinogenesis
Breast
Arachidonate 5-Lipoxygenase
Neoplasms
Cyclooxygenase Inhibitors
Leukotrienes
Incidence
High Fat Diet
Carbon Monoxide
Prostaglandins E

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Abou-El-Ala, S. H., Prasse, K. W., Farrell, R. L., Carroll, R., Wade, A. E., & Bunce, O. R. (1989). Effects of D,L-2-difluoromethylornithine and indomethacin on mammary tumor promotion in rats fed high n-3 and/or n-6 fat diets. Cancer Research, 49(6), 1434-1440.

Effects of D,L-2-difluoromethylornithine and indomethacin on mammary tumor promotion in rats fed high n-3 and/or n-6 fat diets. / Abou-El-Ala, S. H.; Prasse, K. W.; Farrell, R. L.; Carroll, Richard; Wade, A. E.; Bunce, O. R.

In: Cancer Research, Vol. 49, No. 6, 1989, p. 1434-1440.

Research output: Contribution to journalArticle

Abou-El-Ala, SH, Prasse, KW, Farrell, RL, Carroll, R, Wade, AE & Bunce, OR 1989, 'Effects of D,L-2-difluoromethylornithine and indomethacin on mammary tumor promotion in rats fed high n-3 and/or n-6 fat diets', Cancer Research, vol. 49, no. 6, pp. 1434-1440.
Abou-El-Ala, S. H. ; Prasse, K. W. ; Farrell, R. L. ; Carroll, Richard ; Wade, A. E. ; Bunce, O. R. / Effects of D,L-2-difluoromethylornithine and indomethacin on mammary tumor promotion in rats fed high n-3 and/or n-6 fat diets. In: Cancer Research. 1989 ; Vol. 49, No. 6. pp. 1434-1440.
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abstract = "Virgin female Sprague-Dawley rats (50 days of age) were administered a single intragastric 10-mg dose of 7,12-dimethylbenz(a)anthracene (DMBA). Twenty-one days later they were placed on diets containing either 20{\%} corn oil (CO), 15{\%} menhaden oil plus 5{\%} corn oil (MO + CO), 20{\%} CO plus 0.5{\%} w/w of the irreversible ornithine decarboxylase inhibitor, D,L-2-difluoromethylornithine (CO + DFMO), 20{\%} CO plus 0.004{\%} w/w of the cyclooxygenase inhibitor indomethacin (CO + INDO), 20{\%} CO + 0.004{\%} INDO + 0.5{\%} DFMO (CO + INDO + DFMO), or 15{\%} MO + 5{\%} CO + 0.5{\%} DFMO (MO + CO + DFMO). The incidence of DMBA-induced mammary tumors was significantly reduced in rats fed diets containing DFMO but not in rats fed the diet containing indomethacin. Incidences of mammary tumors at 16 weeks post-DMBA were 86{\%} in rats fed the CO diet, 83{\%} in rats ingesting the diet containing CO + INDO, 28{\%} in rats fed CO + DFMO, 32{\%} in rats fed diet containing CO + INDO + DFMO, 59{\%} in rats fed the MO + CO diet, and 24{\%} in rats fed the MO + CO + DFMO diet. The average number of tumors and tumor burden per tumor-bearing rat were reduced and tumor latency was increased in all rats fed diets containing DFMO. Body weight gain, but not food intake, of rats fed the 20{\%} fat + 0.5{\%} DFMO diets was significantly less than in rats fed the 20{\%} fat diets. Prostaglandin E and leukotriene (LTB4) syntheses, ODC activity and mammary tumorigenesis were significantly inhibited by feeding the diet containing menhaden oil or by adding 0.5{\%} DFMO to any of the high fat diets. Feeding a 20{\%} CO diet containing 0.004{\%} INDO significantly reduced prostaglandin synthesis and ODC activity and increased LTB4 synthesis of mammary tumors but did not inhibit mammary tumorigenesis. This study suggests that the 5-lipoxygenase product LTB4 may be involved in mammary tumor production. Whereas a decrease in LTB4 appears to be associated with a decrease in tumorigenesis, an increase (as seen in the indomethacin group) was not associated with any change in the tumorigenic response.",
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T1 - Effects of D,L-2-difluoromethylornithine and indomethacin on mammary tumor promotion in rats fed high n-3 and/or n-6 fat diets

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AU - Wade, A. E.

AU - Bunce, O. R.

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N2 - Virgin female Sprague-Dawley rats (50 days of age) were administered a single intragastric 10-mg dose of 7,12-dimethylbenz(a)anthracene (DMBA). Twenty-one days later they were placed on diets containing either 20% corn oil (CO), 15% menhaden oil plus 5% corn oil (MO + CO), 20% CO plus 0.5% w/w of the irreversible ornithine decarboxylase inhibitor, D,L-2-difluoromethylornithine (CO + DFMO), 20% CO plus 0.004% w/w of the cyclooxygenase inhibitor indomethacin (CO + INDO), 20% CO + 0.004% INDO + 0.5% DFMO (CO + INDO + DFMO), or 15% MO + 5% CO + 0.5% DFMO (MO + CO + DFMO). The incidence of DMBA-induced mammary tumors was significantly reduced in rats fed diets containing DFMO but not in rats fed the diet containing indomethacin. Incidences of mammary tumors at 16 weeks post-DMBA were 86% in rats fed the CO diet, 83% in rats ingesting the diet containing CO + INDO, 28% in rats fed CO + DFMO, 32% in rats fed diet containing CO + INDO + DFMO, 59% in rats fed the MO + CO diet, and 24% in rats fed the MO + CO + DFMO diet. The average number of tumors and tumor burden per tumor-bearing rat were reduced and tumor latency was increased in all rats fed diets containing DFMO. Body weight gain, but not food intake, of rats fed the 20% fat + 0.5% DFMO diets was significantly less than in rats fed the 20% fat diets. Prostaglandin E and leukotriene (LTB4) syntheses, ODC activity and mammary tumorigenesis were significantly inhibited by feeding the diet containing menhaden oil or by adding 0.5% DFMO to any of the high fat diets. Feeding a 20% CO diet containing 0.004% INDO significantly reduced prostaglandin synthesis and ODC activity and increased LTB4 synthesis of mammary tumors but did not inhibit mammary tumorigenesis. This study suggests that the 5-lipoxygenase product LTB4 may be involved in mammary tumor production. Whereas a decrease in LTB4 appears to be associated with a decrease in tumorigenesis, an increase (as seen in the indomethacin group) was not associated with any change in the tumorigenic response.

AB - Virgin female Sprague-Dawley rats (50 days of age) were administered a single intragastric 10-mg dose of 7,12-dimethylbenz(a)anthracene (DMBA). Twenty-one days later they were placed on diets containing either 20% corn oil (CO), 15% menhaden oil plus 5% corn oil (MO + CO), 20% CO plus 0.5% w/w of the irreversible ornithine decarboxylase inhibitor, D,L-2-difluoromethylornithine (CO + DFMO), 20% CO plus 0.004% w/w of the cyclooxygenase inhibitor indomethacin (CO + INDO), 20% CO + 0.004% INDO + 0.5% DFMO (CO + INDO + DFMO), or 15% MO + 5% CO + 0.5% DFMO (MO + CO + DFMO). The incidence of DMBA-induced mammary tumors was significantly reduced in rats fed diets containing DFMO but not in rats fed the diet containing indomethacin. Incidences of mammary tumors at 16 weeks post-DMBA were 86% in rats fed the CO diet, 83% in rats ingesting the diet containing CO + INDO, 28% in rats fed CO + DFMO, 32% in rats fed diet containing CO + INDO + DFMO, 59% in rats fed the MO + CO diet, and 24% in rats fed the MO + CO + DFMO diet. The average number of tumors and tumor burden per tumor-bearing rat were reduced and tumor latency was increased in all rats fed diets containing DFMO. Body weight gain, but not food intake, of rats fed the 20% fat + 0.5% DFMO diets was significantly less than in rats fed the 20% fat diets. Prostaglandin E and leukotriene (LTB4) syntheses, ODC activity and mammary tumorigenesis were significantly inhibited by feeding the diet containing menhaden oil or by adding 0.5% DFMO to any of the high fat diets. Feeding a 20% CO diet containing 0.004% INDO significantly reduced prostaglandin synthesis and ODC activity and increased LTB4 synthesis of mammary tumors but did not inhibit mammary tumorigenesis. This study suggests that the 5-lipoxygenase product LTB4 may be involved in mammary tumor production. Whereas a decrease in LTB4 appears to be associated with a decrease in tumorigenesis, an increase (as seen in the indomethacin group) was not associated with any change in the tumorigenic response.

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