Cancer is one of the longest-known human diseases. The first scientific descriptions are attributed to the Greek Hippocrates, the ‘Father’ of Medicine (≈460–370 BC), to whom the analogy between malignancies and ‘crab’ (with which a Greek wording for cancer, carcinos, is related), due to the projection-like outgrowths of the disease resembling the decapod crustaceans’ locomotory appendages. The Greek physician Galen (130–200 AD), practicing in Rome, first used the term oncos (‘growth’) to describe cancer, which stands today as the prefix of cancer-related terms such as oncogenesis (the complex process by which normal cells transform into cancer cells). Nonetheless, the oldest medical mentions to cancer date back to at least 1600 BC, even though they are likely based on information collected up to a thousand years before, if not more. They were found in ancient Egyptian writing (the ‘Edwin Smith’ and ‘George Ebers’ papyri) that, inclusively, already mentioned treatment by surgery, pharmacology and magic rituals [1,2].

Today, cancer is acknowledged as the principal cause of mortality worldwide, being responsible for about 10 million fatalities annually (with about twice as many new cases per year), figures that, led by in cases and death rate by lung cancer, can only partly be explained by population growth or socioeconomical development, as they may double in the next decade [3]. Even though the exact proportion of chemical-induced cancer is extremely difficult to estimate, Colditz and Wei [4] estimated that, excluding tobacco smoking, it may attain 10%. The same authors also noted that, due to legislation reducing occupational exposure for workers of high-risk industries (such as steel mills) in developed countries from late 20th century onwards, risk can actually be underestimated globally, since a great deal of heavy industry has been transferred to less-developed countries, where cases are likely underreported. Altogether, the incidence of cancer driven or at least co-adjuvated by exposure to pollutants represents a very significant portion of all cases and is seemingly increasing. As suggested by the European Commission Joint Research Centre (EC-JRC), “Public health policy actions cannot be decoupled from environmental policy actions, since exposure to chemicals through air, soil, water and food can contribute to cancer and other chronic diseases” (sic Madia et al. [5]). Needless to say, the challenges of describing and mitigating human health risks are but a fraction of those related to ecosystem and wildlife. Considering that malignancies have been found in 70-million-year-old dinosaur fossils [6], it is safe to assume that cancer is transversal at least among vertebrates, which renders environmental carcinogens not just a key problem for environmental toxicologists in general, but also to ecotoxicologists.

Cancer is essentially a genetic disease. Despite its long record in human medicine, the causes of cancer only began to be understood in the 20th century, especially after the discovery of the role of DNA and its chemistry; first in 1944 with the discovery by Avery et al. [7] that DNA is the ‘transforming principle’ in heredity; then with the famous ‘photo 51′ of Franklin and Gosling [8], which was paramount to the double helix of Watson and Crick [9]. Interestingly, the first human oncogene was only described in the early 1980s [10], following the pioneer work of Duesberg and Vogt [11] on avian retroviruses and transforming factors leading to sarcomas (malignancies of mesodermal-origin tissues, such as sub-dermal connective tissue). Almost immediately, Reddy et al. [12] disclosed molecular events underneath proto-oncogene activation into full oncogene, disclosing that all it may take is a single-point mutation. Quite naturally, this raised important questions among genotoxicologists, as it provided important insights on the mechanisms by which pollutants are oncogenic, even though we know today that different toxicants imply distinct modes-of-action, an issue that will be addressed further on. In the aftermath of these discoveries, just before the end of the 20th century, toxicologists and oncobiologists discovered that certain toxicants can cause specific mutations to oncogenes, leading to up-regulation of oncoproteins and therefore unbalancing cell cycle in favour of proliferation with prejudice of DNA checkpoints, cell cycle arrest and apoptosis; or, conversely, hindering the expression of tumour suppressors such as TP53. One of the most significant discoveries relates to polycyclic aromatic hydrocarbons (PAHs), many of which yield mutagenic metabolites (such as epoxides and some quinones) following phase I bioactivation by CYPs [13]. We now know that the formation of bulky DNA-metabolite adducts is not stochastic. Instead, there are preferential binding sites in specific regions of proto-oncogenes, such as those of the human ras family, promoting mutation due to problems in the removal of these lesions that lead to the conversion of the genes in oncogenes. increasing expression and subsequent up-regulation of oncoproteins (see Ross and Nesnow [14]). Considering the prevalence of PAHs in emissions such as tobacco smoke plus fumes and their particulate matter, this issue has been receiving specific attention due to its implications in human lung cancer (reviewed by Moorthy et al. [15], DeMarini and Linak [16]). The paradigmatic case study of PAH mutagenicity and carcinogenicity illustrates that cell and molecular biology laid important foundations for establishing causation and both human and ecological risk assessment. However, there are other fields of research that revolutionised toxicology and must thus not be forgotten. It is the case of the teachings of the British mathematician turned biologist Ronald Fisher (1890–1962), which, despite being involved mostly in population genetics (he was a polemic advocate of eugenics and endorsed human race distinction), arguably constructed the basis of modern statistics and biostatistics that are paramount for toxicologists and that are in the core of computational biology methods. Similar acknowledgements must be given to epidemiology, environmental chemistry and ecology.

It must be noted that pollutant-induced carcinogenesis in humans is just a small part of a large environmental problem. Even though the nature and function of detoxification phase I/II enzymatic systems and their role in neoplasia in non-vertebrate animals is far from consensual, in large part due to unstable substrate-dependent evolution from common ancestry [17,18], they tend to be well-conserved amongst vertebrates, including fish, which sustains that chemical mutagenesis and oncogenesis are also a serious ecotoxicological problem. In fact, ecotoxicologists have been in the frontline of research and are responsible for major developments in risk assessment, biomarker plus bioassay development and toxicogenomics. This contribution owes much to the fact that ecotoxicologists have to deal with challenges like toxicant mixtures in intricate matrices (such as natural sediments); unconventional model species with reduced or absent genomic annotation and unaccountable noise variables compromising causation [13,19,20].

2. A Brief Historical Overview of Cancer and Pollution