Adverse health effects of environmental chemical agents through non-genotoxic mechanisms

• Published in: Journal of epidemiology and community health (1979) Vol. 65; no. 1; pp. 1 - 3
• Main Authors: Henkler, Frank, Luch, Andreas
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.01.2011; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Adipose tissue; Adverse effects; Apoptosis; Apoptosis - drug effects; Arsenic; Carcinogenesis; Carcinogens - pharmacology; Carcinogens - toxicity; Cell adhesion & migration; Cell cycle; Chemical agents; Chemical hazards; Chemicals; DNA methylation; Editorial; Endocrine Disruptors - adverse effects; Environmental effects; Environmental Exposure - adverse effects; Epigenetics; Food chains; Health risks; Homeostasis; Hormones; Humans; Hypoxia; Kinases; Ligands; Neoplasia; Neoplasms - chemically induced; PCB; Pesticides; Physiology; Polychlorinated biphenyls; Proteins; Reactive oxygen species; Receptors; Signal Transduction - drug effects; Superoxides; Thyroid; Thyroid gland; Toxicology; Tumors; Xenobiotics; Xenobiotics - pharmacology
• ISSN: 0143-005X; 1470-2738
• DOI: 10.1136/jech.2008.083881

Many of these compounds are now suspected or have already been demonstrated to be capable of modulating cellular receptor responses involved in physiological signal cascades by mimicking or counteracting endogenous receptor ligands. Besides typical hormone receptors-such as those that govern cellular responses to physiological levels of oestrogens, androgens, progesterone, glucocorticoids, mineralocorticoids and thyroid hormones-many others were characterised, including those involved in xenobiotic recognition and responses. 1 In terms of toxicology, most important among the latter so-called 'xenosensors' are the arylhydrocarbon receptor (AHR), the pregnane X receptor and the constitutive androstane receptor. [...]a whole range of different adverse effects can be anticipated; many of them address multiple hormone-sensitive systems simultaneously. 5 For example, the earlier onset of female puberty, increased sensitivity of adipose tissue towards insulin, obesity, and neuronal developmental damage had previously been linked to various EDC; these effects urgently require further clarification.\n 12 Apoptotic resistance It is well known from chemotherapy that exposure to genotoxic drugs can induce resistance towards apoptosis in the cells treated.