GLOBAL METHYLATION PATTERN CHANGES IN BREAST AND COLORECTAL CANCER CELLS TREATED WITH DIFFERENT CHEMOTHERAPEUTIC DRUGS

Cancer in a global threat as it is considered the primary cause of death worldwide. Breast cancer is the most common cancer I female worldwide. In the present study we evaluated the role of temozolomide, carboplatin, sodium phenylbutyrate, and cyclophosphamide in changing the methylation landscape of four tumor cell liness; breast, colorectal, lung, and cervical. Cells were treated with 5 µM of each drug and the cells were incubated with the drugs for 48 and 96 h before reading the changes in methylation patterns. Global methylation quantification was measured in cells after being treated with the drugs. Data obtained indicated that sodium phenylbutyrate, followed by temozolomide were the drugs most efficient in hypermethylation of the DNA, while carboplatin followed by cyclophosphamide were able to reduce the concentration of 5-mC in the DNA. It has been concluded that using carboplatin in combination with sodium phenylbutyrate (PBA) might induce cell cycle arrest of malignant cells. Further studies are needed to highlight the mechanism of action of these drugs when combined in treatment of cancer. Keywords: methylation; breast; colon; lung; cervical; epigenetics

Antigenotoxic Studies of Different Substances to Reduce the DNA Damage Induced by Aflatoxin B1 and Ochratoxin A

Mycotoxins are produced mainly by the mycelial structure of filamentous fungi, or more specifically, molds. These secondary metabolites are synthesized during the end of the exponential growth phase and appear to have no biochemical significance in fungal growth and development. The contamination of foods and feeds with mycotoxins is a significant problem for the adverse effects on humans, animals, and crops that result in illnesses and economic losses. The toxic effect of the ingestion of mycotoxins in humans and animals depends on a number of factors including intake levels, duration of exposure, toxin species, mechanisms of action, metabolism, and defense mechanisms. In general, the consumption of contaminated food and feed with mycotoxin induces to neurotoxic, immunosuppressive, teratogenic, mutagenic, and carcinogenic effect in humans and/or animals. The most significant mycotoxins in terms of public health and agronomic perspective include the aflatoxins, ochratoxin A (OTA), trichothecenes, fumonisins, patulin, and the ergot alkaloids. Due to the detrimental effects of these mycotoxins, several strategies have been developed in order to reduce the risk of exposure. These include the degradation, destruction, inactivation or removal of mycotoxins through chemical, physical and biological methods. However, the results obtained with these methods have not been optimal, because they may change the organoleptic characteristics and nutritional values of food. Another alternative strategy to prevent or reduce the toxic effects of mycotoxins is by applying antimutagenic agents. These substances act according to several extra- or intracellular mechanisms, their main goal being to avoid the interaction of mycotoxins with DNA; as a consequence of their action, these agents would inhibit mutagenesis and carcinogenesis. This article reviews the main strategies used to control AFB1 and ochratoxin A and contains an analysis of some antigenotoxic substances that reduce the DNA damage caused by these mycotoxins