Fermented foods are among the food products more often complained of having caused episodes of biogenic amines (BA) poisoning. Concerning milk-based fermented foods, cheese is the main product likely to contain potentially harmful levels of BA, specially tyramine, histamine, and putrescine. Prompted by the increasing awareness of the risks related to dietary uptake of high biogenic amine loads, in this review we report all those elaboration and processing technological aspects affecting BA biosynthesis and accumulation in dairy foods. Improved knowledge of the factors involved in the synthesis and accumulation of BA should lead to a reduction in their incidence in milk products. Synthesis of BA is possible only when three conditions converge: (i) availability of the substrate amino acids; (ii) presence of microorganisms with the appropriate catabolic pathway activated; and (iii) environmental conditions favorable to the decarboxylation activity. These conditions depend on several factors such as milk treatment (pasteurization), use of starter cultures, NaCl concentration, time, and temperature of ripening and preservation, pH, temperature, or post-ripening technological processes, which will be discussed in this chapter.

Tyramine and histamine, the most toxic biogenic amines (BA), are often found in high concentrations in certain foods. Prompted by the limited knowledge of BA toxicity, and increasing awareness of the risks associated with high intakes of dietary BA, the in vitro cytotoxicity of tyramine and histamine was investigated. Tyramine and histamine were toxic for HT29 intestinal cell cultures at concentrations commonly found in BA-rich food, as determined by real-time cell analysis. Surprisingly, tyramine had a stronger and more rapid cytotoxic effect than histamine. Their mode of action was also different, while tyramine caused cell necrosis, histamine induced apoptosis. To avoid health risks, the BA content of foods should be reduced and legal limits established for tyramine.

Melatonin is an indole hormone produced mainly by the pineal gland. We have previously demonstrated that melatonin interferes with estrogen (E 2 ) signaling in MCF7 cells by impairing estrogen receptor (ER) pathways. Here we present the characterization of its mechanism of action showing that melatonin is a specific inhibitor of E 2 -induced ER␣-mediated transcription in both estrogen response element-and AP1-containing promoters, whereas ER␤-mediated transactivation is not inhibited or even activated at certain promoters. We show that the sensitivity of MCF-7 cells to melatonin depends on the ER␣/ER␤ ratio, and ectopic expression of ER␤ results in MCF-7 cells becoming insensitive to this hormone. Melatonin acts as a calmodulin antagonist inducing conformational changes in the ER␣-calmodulin (CaM) complex, thus impairing the binding of E 2 ⅐ER␣⅐CaM complex to DNA and, therefore, preventing ER␣-dependent transcription. Moreover the mutant ER␣ (K302G,K303G), unable to bind calmodulin, becomes insensitive to melatonin. The effect of melatonin is specific since other related indoles neither interact with CaM nor inhibit ER␣-mediated transactivation. Interestingly, melatonin does not affect the binding of coactivators to ER␣, indicating that melatonin action is different from that of current therapeutic anti-estrogens used in breast cancer therapy. Thus, they target ER␣ at different levels, representing two independent ways to control ER␣ activity. It is, therefore, conceivably a synergistic pharmacological effect of melatonin and current anti-estrogen drugs.Melatonin is an indole hormone that is the major secretory product of the pineal gland. The most clearly defined actions of melatonin have been demonstrated on the reproductive system of seasonally breeding animals and on circadian rhythms and sleep. A rapidly emerging avenue of investigation is the oncostatic and anti-proliferative effects of melatonin on endocrineresponsive neoplasms, especially in those concerning the mammary gland (1). The most common conclusion in animal models of tumorigenesis is that either experimental manipulations that activate the pineal gland or the administration of melatonin reduces the incidence and development of chemically induced mammary tumors, whereas pinealectomy usually stimulates breast cancer growth (2-4). Epidemiological studies have shown a low incidence of breast tumors in blind women as well as an inverse relationship between breast cancer incidence and the degree of visual impairment. Because light inhibits melatonin secretion, the increase in melatonin-circulating levels might be interpreted as proof of the protective role of this hormone on mammary carcinogenesis (5). A moderate increase in breast cancer risk among women who worked extended periods of rotating night shifts (light exposure during night suppresses melatonin production) has also been described (6).Different mechanisms have been proposed to explain how melatonin could reduce the development of mammary tumors; they are indirect neuroendocrine mechanisms ...

The consumption of food and beverages containing high amounts of biogenic amines (BA) can have toxicological effects. BA found in foods and beverages are synthesized by the microbial decarboxylation of certain amino acids. This paper reports the concentrations of BAs in a number of commercial cheeses, as determined by HPLC. The cheeses studied were made from raw and pasteurized milk of different origin, and were subjected to different ripening periods. BA concentrations were lower in short ripening period than in long ripening period cheeses, and higher in cheeses made from raw milk than in those made from pasteurized milk. The highest BA concentrations were recorded in blue cheeses made from raw milk. Tyramine was the most commonly recorded and abundant BA. The presence of tyramine-producing bacteria was determined by PCR, and a good correlation obtained between the results of this method and tyramine detection by HPLC. These methods could be used to complement one another in the detection and quantification of tyramine in cheese prevention of tyramine accumulation in cheese.

Putrescine and cadaverine are among the most common biogenic amines (BA) in foods, but it is advisable that their accumulation be avoided. Present knowledge about their toxicity is, however, limited; further research is needed if qualitative and quantitative risk assessments for foods are to be conducted. The present work describes a real-time analysis of the cytotoxicity of putrescine and cadaverine on intestinal cell cultures. Both BA were cytotoxic at concentrations found in BA-rich foods, although the cytotoxicity threshold for cadaverine was twice that of putrescine. Their mode of cytotoxic action was similar, with both BA causing cell necrosis; they did not induce apoptosis. The present results may help in establishing legal limits for both putrescine and cadaverine in food.