Tumorigenic effect mediated by ROS/eicosanoids and their regulation on TP53 expression in a murine mammary gland adenocarcinoma.

The aim of this study was to investigate the in vivo and in vitro effects of dietary ω-6 and ω-3 polyunsaturated fatty acids (PUFAs) and their derivatives on the expression of TP53 and their relationship with cellular proliferation and death in a murine mammary adenocarcinoma model. BALB/c mice were divided in three diet groups: chia oil (ChO) rich in ω-3, corn oil (CO) rich in ω-6/ω-3 and safflower oil (SO) rich in ω-6 and subcutaneously inoculated with LMM3 mammary tumor cell line. Results demonstrated that diets with higher concentration of omega-6 PUFAs induced an increment of linoleic and arachidonic acid on tumor cell membranes increasing ROS liberation, 12(S)-HHT generation, TP53, Ki67 expression and cell proliferation. However, diets enriched with high content in omega-3 PUFAs induced higher tumor cell apoptosis and tumor infiltration of CD3+ lymphocytes, lowest cell viability and proliferation. Dietary omega-3 PUFAs nutritional intervention can be used as a potential preventative strategy to inhibit the molecular signaling pathways involved in the mammary tumor growth process as the TP53.

Effect of the co-administration of phenobarbital, quercetin and mancozeb on nitrosomethylurea-induced pancreatic tumors in rats.

UNLABELLED: We have previously shown that a single i.p. injection of nitrosomethylurea (NMU) in 3-day-old rats orally treated with the pesticide mancozeb (MZ), the flavonoid quercetin (Q) or in combination (MZ-Q) induces hyperplasia, atypical acinar cell proliferation and carcinoma in situ (CIS) in the pancreas. This work studies the effect of oral administration of phenobarbital (PB) on this model of pancreatic carcinogenesis. The animals were fed on a diet supplemented by MZ or/and Q from the 10th day of pregnancy, thorough lactation and as pups after weaning until being sacrificed at week 24. Saline injection with non-supplemented diet was used for the control group (SAL). The experimental groups were (1) SAL (control), (2) SAL-PB, (3) NMU, (4) NMU-PB, (5) MZ-NMU, (6) MZ-NMU-PB, (7) Q-NMU, (8) Q-NMU-PB, (9) MZ-Q-NMU and (10) MZ-Q-NMU-PB. Acinar cell hyperplasia was found in all groups of NMU-treated rats. Dysplastic foci (DYS) were seen in groups 3-10 at the following percentages: 19, 48, 71, 27, 71, 35, 100 and 30, respectively. CIS were recorded in groups 4 to 10 at percentages: 4, 36, 13, 11, 0, 16, 5, respectively. CONCLUSION: Although PB, Q or MZ given alone enhance DYS lesions in NMU-treated rats, the MZ/Q/PB combined treatments may increase (mainly in males) or decrease (mainly in female) the DYS and CIS proportion. Because PB, MZ and Q influence P450 enzymes, we suggest that these enzymes play a role in the carcinogenesis process.

Quercetin enhances pretumorous lesions in the NMU model of rat pancreatic carcinogenesis.

The effect of dietary quercetin (Q) was evaluated in rats treated with nitrosomethylurea (NMU). Pancreatic nodules and focal acinar cell hyperplasias were observed in groups treated with NMU (87%) and Q-NMU (100%). Although rats with dysplastic foci (27%) were found in the NMU-treated group, Q-NMU treatment resulted in a significantly higher number of rats with dysplastic foci (73%). Furthermore, carcinomas in situ (12%) and one microcarcinoma (4%) were found in these animals. Mitosis was significantly increased and apoptosis was diminished in focal acinar cell hyperplasias of the Q-NMU group. Our present results support a promoting and progressing effect of quercetin in the NMU model of rat pancreatic carcinogenesis.

Morphological and biological characterization of two mesenchymal murine tumors and the modulation of their growth parameters by n-3 and n-6 polyunsaturated fatty acids.

Certain tumor growth parameters (GP) of two mesenchymal transplantable tumors maintained on C57BL/6J mice were characterized. Considering that many experimental, clinical and epidemiologic data have indicated that n-3 and n-6 essential fatty acids are nutrients which may delay the development as well as improve the course of cancer, GPs were evaluated on hosts fed on a semisynthetic formula containing 5% of corn oil (CO) or cod liver oil (CLO) and stock diet (C group). Although survival and latency time of tumor-bearing mice were shortened, other GP as percentage of successful implants were improved by both oils in sarcoma-bearing hosts, suggesting that n-3 and n-6 fatty acids might play a modulating role for the development of these tumors.