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  • Title: II. Effect of n-3 and n-6 fatty acids on mammary H-ras expression and PGE2 levels in DMBA-treated rats.
    Author: Karmali RA, Chao CC, Basu A, Modak M.
    Journal: Anticancer Res; 1989; 9(4):1169-74. PubMed ID: 2510583.
    Abstract:
    In an attempt to evaluate some of the mechanisms by which dietary n-3 and n-6 PUFA influence 7,12,dimethylbenz(a)anthracene (DMBA)-induced mammary tumorigenesis, we measured: 1) concentrations of prostaglandin (PG) E1 (metabolite of C20:3, n-6) and PGE2 (metabolite of C20:4, n-6); and, 2) expression of H-ras oncogene in non-cancerous (NC) and cancerous (C) mammary tissues taken from rats 14 weeks after they were treated with 5 mg DMBA. Five groups of rats were fed one of the synthetic diets containing 23.5% of fat by weight: I. Blackcurrant oil (BCO) (23.5%); II. corn oil (CO) (23.5%); III. BCO (15.5%) + fish oil (FO) (8%); IV. FO (20.5%) + CO (3%); and V. BCO (20.5%) + FO (3%). PGE1 and PGE2 levels were lower in NC mammary tissues than in corresponding C tissues in all 5 diet groups. In Group IV, PGE2 levels in both NC and C tissues were significantly lower than in those of the remaining 4 groups. In groups fed BCO alone (I) or in combination with FO (III and V), PGE2, content in C tissue was lower compared with the corn oil-fed group (II), but these observations were significant only for III and V. Conversely, in Groups III and V, the content of PGE1 in C tissues was significantly higher. The results of the present study demonstrate interactions and competition between 3 eicosapolyenoic acids that act as substrates for cyclooxygenase. The observation that PGE2 production is reduced when mammary tumor development was inhibited confirms earlier findings. Whether these changes in eicosanoids can explain differences in ras p21 levels as judged by cross-linking to a-32 P-GTP remains to be investigated in greater detail. Preliminary results from a small number of samples indicate that expression of H-ras in C mammary tissue was in the order CO (II) greater than BCO (I) = FO (IV).
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