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(18-22) Carcinogenesis in the light of endocrine disruption. Amaral-Mendes, Jose*,1, Pluygers, Eric2, Sadowska, Ala3, 1 University of Evora, Evora, Evora, Portugal2 Jolimont Hospital(Honorary Oncologist), La Louviere, Belgium3 Agricultural University, Warsaw, Poland ABSTRACT- Ever since the observation of "soot cancers" on the scrotum of chimney- -sweeps and of "tar cancers" in asphalt workers and in experimental settings has haunted the scientific community in the query for the understanding of the mechanisms underlying carcinogenesis. This search has resulted, in the 1950s, in the acceptance of the "multistage carcinogenesis" concept, giving credit to the development of several sequential "phases": initiation, promotion, progression and finally malignancy. Initiation being enforced by mutagenicity, a series of assays was developed to assess the mutagenicity of suspected carcinogenic compounds, until it became apparent that "carcinogenesis was more than mutagenesis". Indeed, many carcinogens acting at later phases appeared to possess no mutagenic activity at all, but to be acting through a maze of cellular effects that had imperatively to be taken into consideration in evaluating the carcinogenic process. To omit these factors, as has often occurred with the aim of oversimplifying complex matters, is inadmissible and leads to erroneous conclusion. Abundant information is presently available regarding topics such as oncogenes, tumour suppressor genes, growth factors and their receptors, intracellular second messengers and a series of accessory mechanisms all of which contribute to the induction of low-dose effects some of them at the level of one molecule of a contaminant. The advent of Endocrine Disruptors prone to modulate physiological effects rather than to induce toxicity, has not simplified the question. The effects are often intricate, depending on interactions between several endocrine systems, and effects believed to be simple in origin may, in fact, be generated at very different levels. For instance in the case of estrogenicity, the effect is not only dependent on binding with the intracellular Estrogen Receptor, but also on binding with an unrelated membrane receptor, and on induction of aromatase, the enzyme converting androgens into estrogens. A comprehensive evaluation of estrogenicity will necessitate to consider all those different mechanisms without any improper oversimplification. Key words: endocrine disruptors, carcinogeneseis |
