Re: Omega-3 beats Omega-6 in metastasis promotion !

"despite decreased PGE2 productio" ...

Nutr Cancer. 1998;30(2):137-43.

Effects of dietary n-3-to-n-6 polyunsaturated fatty acid ratio on
mammary carcinogenesis in rats.

Sasaki T, Kobayashi Y, Shimizu J, Wada M, In'nami S, Kanke Y, Takita
T.
Division of Bioregulation Studies, Tokyo University of Agriculture,
Japan.

We investigated the effects of the dietary n-3-to-n-6 polyunsaturated
fatty acid (PUFA) ratio (n-3/n-6 ratio) on mammary carcinogenesis
induced by 7,12-dimethylbenz[a]anthracene in rats by feeding them
several types of dietary fat with a fixed PUFA-to-saturated fatty acid
ratio. Dietary fat was fed to the rats as 10% of the total feed
weight, starting two weeks before the initiation. An increase in the
n-3/n-6 ratio did not suppress the incidence or reduce the latency of
mammary tumor development. The number and weight of mammary tumors per
tumor-bearing rat tended to be large in the group with an n-3/n-6
ratio of 7.84 compared with those in the other groups. As the n-3/n-6
ratios were elevated, the total number and weight of tumors increased
gradually. The prostaglandin E2 (PGE2) concentration in mammary tumor
tissue was markedly low in the group with an n-3/n-6 ratio of 1.03
compared with the group with an n-3/n-6 ratio of 0.01. In addition,
PGE2 concentrations were almost constant when n-3/n-6 ratios were >
1.03. These results suggested that the increase in the n-3/n-6 ratio
of dietary fat with the fixed PUFA-to-saturated fatty acid ratio
cannot suppress the mammary carcinogenesis but can promote development
of tumors, despite reduced PGE2 concentration in the tumor.
PMID: 9589432


Carcinogenesis. 2005 Sep;26(9):1563-72. Epub 2005 May 11.

Opposing effects of prepubertal low- and high-fat n-3 polyunsaturated
fatty acid diets on rat mammary tumorigenesis.

Olivo SE, Hilakivi-Clarke L.
Lombardi Comprehensive Cancer Center, Georgetown University, 3970
Reservoir Road NW, Washington, DC, USA.

To determine whether dietary fat intake during childhood affects the
later risk of developing breast cancer, we fed prepubertal rats
between post-natal days 5 and 25 a low (16% energy) or high-fat (39%
energy) diet composed mainly of n-6 or n-3 polyunsaturated fatty acids
(PUFAs) originating either from corn oil or menhaden oil,
respectively, in the ratios of 16-17:1 (n-6 PUFA diets) or 2-3:1 (n-3
PUFA diets). We also examined whether changes in risk are associated
with perturbations in biological processes previously linked to fatty
acid intake and breast cancer. Mammary tumorigenesis was induced by
treating 50-day-old rats with the carcinogen 7,12-
dimethylbenz[a]anthracene. When compared with the reference low-fat
n-6 PUFA diet, prepubertal exposure to the low-fat n-3 PUFA diet
decreased, whereas a high-fat n-3 PUFA diet increased mammary tumor
incidence; the high-fat n-6 PUFA diet had no effect. Both the low and
high-fat n-3 PUFA diets induced mammary epithelial differentiation by
reducing the number of terminal end buds (TEBs) and increasing the
presence of lobulo-alveolar structures. They also increased lipid
peroxidation and reduced cyclooxygenase-2 activity. Prepubertal
exposure to the low-fat n-3 PUFA diet increased apoptosis, determined
using TUNEL assay, and reduced cell proliferation, determined using
PCNA staining. In marked contrast, prepubertal exposure to the high-
fat n-3 PUFA diet induced cell proliferation and inhibited apoptosis
in the TEBs and lobular structures. The latter is consistent with the
finding that pAkt, a survival factor that inhibits apoptosis, was
elevated in their mammary glands. In summary, although prepubertal
exposure to a low-fat n-3 PUFA diet reduced later mammary
tumorigenesis in rats, high levels of this fatty acid can have adverse
effects on the prepubertal mammary gland and increase subsequent
breast cancer risk.
PMID: 15888492
.