Studying the environmental chemicals to assess their long-term carcinogenic potential

Every year, cancer is the cause for more than 8 millions of deaths worldwide; and every day, scientists from all countries put all their efforts into trying to understand a little bit more this disease. The process of a tumor formation is very complicated due to the great amount of factors involved in it. Inheritance plays a very important role but also does the environment: ¿What kind of are carcinogenic factors (chemical substances and physical agents) are we exposed to? ¿Which is the quantity? A large number of studies have been carried out for this purpose but the results are often inconclusive: there may be factors involving cancer development that are not being taken into account. Recently, the World Health Organisation (WHO) together with the International Agency for Research on Cancer (IARC)carried out a study where environmental chemicals werepresented to be the cause of cancer in a 7 to 19 % proportion. However, 174 international experts, including Dr. Matilde Lleonart from theOncology and Molecular Pathology group at Vall d’Hebron Institute of Research (VHIR), and Dr. Laura Soucek and Johnatan Whitfield from the Mouse Models of Cancer Therapies Group from VHIO, have reviewed this study. According to the article, which is published in the Carninogenesis journal, chemical agents present in the environment were involved in a higher proportion of cancers but the relationship between doses to which we are exposed and the risk for developing the disease may be complicated.

The study presented by the WHO and IARC consisted of assessing the effect of multiple environmental chemical substances on cells. The analysis was performed on a substance-by-substance basis; the aim was to watch and determine the amount of dose required to start producing in the cell the mechanisms involved in cancer development. Taking into account all we know about cancer nowadays, the reviewers state that the approach of this study may not be the correct one: we do not get exposed to carcinogens in isolation, one by one, but potentially toxic substances present in the environment can act synergistically to develop cancer. “There are lots of chemicals in the environment impossible to avoid. These substances, even in low-dose exposures, may produce small effects that, when combined, may be involved in cancer development. Assessing chemicals one by one does not keep up with all we know today about cancer. Every day we are exposed to a large amount of environmental chemicals and we have to evaluate the effect of this mixture”, explains William Goodson III, researcher at California Pacific Medical Centre and review's lead author.

Of all the chemicals studied, 85 were reviewed in this study with the purpose of evaluating the carcinogenic potency of substances in conditions similar to real exposure. The effects of low-dose exposure were assessed but making mixtures of various chemicals and over long periods of time. As a result, 50 of the 85 substances that were studied had an effect on cells in low-dose exposures. “The dose required for a substance to have an effect on cells depends on the host of genetic and epigenetic factors that were previously altered”, explains Dr. Lleonart. She also explains that cell type in another differential factor: “The chemical will produce more or less alteration in a cell depending on the type of cell: normal cell, embryonic cell, senescent cell or immortal cell; for this reason it is important to create animal and cell models that can take into account these aspects”. The field of research where Dr. Lleonart is working consists of the relationship between cellular senescence (cellular aging) and prevention of tumorigenesis. Tumor formation is induced by cells that are able to avoid senescence to become immortal. “We have to study combinations of chemicals in each type of cell in order to understand which combinations and doses are required to be lethal”, Dr. Lleonart concludes.