Final Activity Report Summary - FLORE D-SOS CCC (Dietary sources of oxidative stress and their consequences on colon cancer)
Colorectal cancer is the leading cause of cancer death in European non-smokers: more than one thousand new colon cancers are detected daily in Europe, and 570 European people die of it every day. Dietary changes might reduce this cancer incidence up to 70 %, according to epidemiological reports. However, dietary factors that actually initiate the cancer process, and precise dietary changes needed to reduce cancer incidence, are not known. This summary reports the major results of a three-year research project (a Marie Curie grant) that was supported by funding under the Sixth Research Framework Programme of the European Union.
The major finding is that eating an over-cooked diet induces important changes in the colon of rats. These changes (precancerous lesions, increased proliferation, crypts with more cells and changed shape) suggest that an overcooked diet is an important risk factor for colon cancer. In contrast, vitamin B1 deficiency does not induce precancerous lesions in the colon of rats, and the above-cited changes are not due to the destruction of vitamin by cooking. These results are explained in more detail below.
Before the present research was undertaken, it had been known that rats given a diet with reduced thiamin (vitamin B1) for four months have small patches in their colons, ACF, that are recognised as precursors to colon cancer. Furthermore, the toxic effects of reduced thiamin are markedly worse when the cells are exposed to an oxidative stress. Within the frame of the present research a large scale long term study was undertaken in rats given diets with various thiamin levels. In contrast with the starting hypothesis, rats given a thiamin-deficient diet did not had more colonic ACF than controls, although the vitamin deficiency induced markers of oxidative stress in rats' blood. From the point of view of cancer prevention, this study does not tell that vitamin B1 recommended nutrient intakes should be increased.
Many foods we eat are cooked, and some people in Europe eat mostly high-temperature fried and baked foods. It is known that the crust of fried meat contains carcinogenic heterocyclic amines, but the heating of other foods may also produce unknown carcinogens. We thus undertook three studies where heated diets (with no meat) were given to rats. Chemical analysis of the diets showed lower vitamin contents, increased glycated proteins, lipoperoxide and other reactive species, without formation of heterocyclic amines. Such diets induced ACF in two independent studies, using different processing conditions. A third study, with a different composition and cooking, showed strong mucosal dysplasia.
In a third series of studies, the effect of various processed meat was tested in rats previously initiated with a chemical carcinogen. The meat products were either obtained from grocery stores or made on purpose as model foods. Several biomarkers (fecal and urinary malondialdehyde, TBARs, hexanal, 4-hydroxynonenal, 8-iso-prostaglandin-F(2)alpha, and 1,4-dihydroxynonane mercapturic acid) were tested in correlation to the carcinogenic outcome of the third thermolysis study. These studies clearly showed that pork meat that had been treated like a cooked ham could enhance colon carcinogenesis in rats at an early stage.
Last we also showed that analysis of faecal waters and urine (cytotoxicity, presence of reactive by-products like lipoperoxide) was closely associated with the mucosal changes in both cooked foods and processed meat studies. This biomarkers that can be measured in easily available fluids could also be used in human volunteers' studies to assess the pro-carcinogenic effect of specific diets or foods.
The major finding is that eating an over-cooked diet induces important changes in the colon of rats. These changes (precancerous lesions, increased proliferation, crypts with more cells and changed shape) suggest that an overcooked diet is an important risk factor for colon cancer. In contrast, vitamin B1 deficiency does not induce precancerous lesions in the colon of rats, and the above-cited changes are not due to the destruction of vitamin by cooking. These results are explained in more detail below.
Before the present research was undertaken, it had been known that rats given a diet with reduced thiamin (vitamin B1) for four months have small patches in their colons, ACF, that are recognised as precursors to colon cancer. Furthermore, the toxic effects of reduced thiamin are markedly worse when the cells are exposed to an oxidative stress. Within the frame of the present research a large scale long term study was undertaken in rats given diets with various thiamin levels. In contrast with the starting hypothesis, rats given a thiamin-deficient diet did not had more colonic ACF than controls, although the vitamin deficiency induced markers of oxidative stress in rats' blood. From the point of view of cancer prevention, this study does not tell that vitamin B1 recommended nutrient intakes should be increased.
Many foods we eat are cooked, and some people in Europe eat mostly high-temperature fried and baked foods. It is known that the crust of fried meat contains carcinogenic heterocyclic amines, but the heating of other foods may also produce unknown carcinogens. We thus undertook three studies where heated diets (with no meat) were given to rats. Chemical analysis of the diets showed lower vitamin contents, increased glycated proteins, lipoperoxide and other reactive species, without formation of heterocyclic amines. Such diets induced ACF in two independent studies, using different processing conditions. A third study, with a different composition and cooking, showed strong mucosal dysplasia.
In a third series of studies, the effect of various processed meat was tested in rats previously initiated with a chemical carcinogen. The meat products were either obtained from grocery stores or made on purpose as model foods. Several biomarkers (fecal and urinary malondialdehyde, TBARs, hexanal, 4-hydroxynonenal, 8-iso-prostaglandin-F(2)alpha, and 1,4-dihydroxynonane mercapturic acid) were tested in correlation to the carcinogenic outcome of the third thermolysis study. These studies clearly showed that pork meat that had been treated like a cooked ham could enhance colon carcinogenesis in rats at an early stage.
Last we also showed that analysis of faecal waters and urine (cytotoxicity, presence of reactive by-products like lipoperoxide) was closely associated with the mucosal changes in both cooked foods and processed meat studies. This biomarkers that can be measured in easily available fluids could also be used in human volunteers' studies to assess the pro-carcinogenic effect of specific diets or foods.