Assessing the Carcinogenic Potential of Low-Dose Exposures to Chemical
Mixtures in the Environment: The Challenge Ahead – Oxford Journals
Volume 36 Suppl 1 June 2015
Cocktail of common chemicals may trigger cancer: Fifty chemicals the public is exposed to on a daily basis may trigger cancer when combined — ScienceDaily
The research is now published in a special series of Oxford University Publishing’s Carcinogenesis journal on Tuesday 23 June (http://carcin.oxfordjournals.org/content/36/Suppl_1). William Goodson III, a senior scientist at the California Pacific Medical Center in San Francisco and lead author of the synthesis said: “We are definitely concerned that we are now starting to see evidence of a wide range of low dose effects that are directly related to carcinogenesis, exerted by chemicals that are unavoidable in the environment.â€
Antioxidant defense systems as a first line of defense
The main antioxidant defenses are: glutathione [a sulfhydryl- rich compound that binds reactive oxygen species (ROS) and free radical intermediates], enzymes linked to glutathione (such as glutathione peroxidase), superoxide dismutase (breaking down superoxide into H2O2 and oxygen) and catalase (breaking down H2O2). These â€˜caretakersâ€™ are generally effective, but if ROS are present in excess, they can overwhelm the cellular defenses and lead to â€˜oxidative stressâ€™ (62,63). Phase I and phase II metaboliz- ing enzymes play a crucial role in eliminating toxic chemicals from the body. Phase I enzymes (P450 cytochromes, also known as mixed function oxidases) typically oxidize xenobiotics to a reactive form, whichâ€”with the help of phase II enzymes such as glutathione S-transferaseâ€”is then conjugated to a carrier mol- ecule such as glutathione and eliminated (64). However, as a side effect, the phase I enzymes are also responsible for activating certain non-carcinogenic chemicals to form DNA-reactive mol- ecules that can potentially induce mutations. Polymorphisms in genes coding for these enzymes are very common, and so indi- viduals can vary significantly in their resistance to the effects of genotoxic chemicals.
Carcinogenesis is joining this debate by publishing in this issue a series of reviews on the carcinogenic potential of exposure to low doses and mixtures of chemicals. The reviews utilize a framework of the Hallmarks of Cancer (9) and are the product of the Halifax Project Task Force initiated by Leroy Lowe and Michael Gilbertson. They engaged international teams with input of nearly 200 cancer biologists and toxicologists to review the literature in each of the 11 Hallmarks of Cancer. The reviews are multiauthored, condensed by a peer review and extensively referenced. The primary recommendation is a research and regulatory strategy using the Hallmarks of Cancer framework to identify priority mixtures of chemicals, i.e. â€˜â€¦.those with substantial carcinogenic relevanceâ€™, for future investigations â€˜â€¦. to inform risk assessment practices worldwideâ€™ (10).
Carcinogenesis will also publish a review of cancer prevention this summer, which will be written by Christopher Wild, Director of the International Agency on Research of Cancer.
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Emi Miller, RN, HN-BC, ND, ABT, NCCAOM, L.Ac