SummaryLow-dose exposures to common environmental chemicals that are deemed safe individually may be combining to instigate carcinogenesis, thereby contributing to the incidence of cancer. This risk may be overlooked by current regulatory practices and needs to be vigorously investigated.

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Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis.

Relationships between alterations in the profile of urinary arsenic (As) species and the presence of cutaneous signs of arsenicism were studied in Region Lagunera, Mexico. The use of urinary concentrations of putative substrates and products of the As metabolism pathway, as indicators of metabolic efficiency is also discussed. Arsenic was determined by hydride generation atomic absorption spectrophotometry and separation of As species was performed by ion exchange chromatography. The exposed group had an average of 0.408 mg As/l of total As (TAs) in their drinking water, whereas "control' individuals had 0.031 mg/l. Urinary concentrations of arsenic species and TAs were 20 to 95 times higher in the exposed group. Significant increases in the relative proportions of inorganic arsenic (Asi) and monomethylarsonic acid (MMA), accompanied by decreases of dimethylarsinic acid (DMA) were also found in exposed individuals. Therefore, significant decreases in the value of the MMA/Asi, DMA/MMA and DMA/ Asi ratios were observed, suggesting a decreased As methylating ability. Exposed individuals bearing cutaneous signs had a significantly longer time of exposure, higher urinary concentrations and proportions of MMA and MMA/Asi values, and significantly lower DMA/ MMA than exposed individuals without cutaneous signs. Further research is needed to identify better parameters for assessing the efficiency of As metabolism in chronically exposed populations and to confirm the potential relationship between metabolic alterations and overt signs of As toxicity.

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Micronucleus (MN) is a biomarker widely used in biomonitoring studies carried out to determine the genetic risk associated to pesticide exposure. Many in vitro and in vivo studies, as well as epidemiological approaches, have demonstrated the ability of certain chemical pesticides to produce genetic effects including cancer and other chronic pathologies in humans; thus, biomonitoring studies have been carried out to characterise the genetic risk associated to pesticide exposure. It must be noted that 'pesticide exposure' is a broad term covering complex mixtures of chemicals and many variables that can reduce or potentiate their risk. In addition, there are large differences in pesticides used in the different parts of the world. Although pesticides constitute a wide group of environmental pollutants, the main focus on their risk has been addressed to people using pesticides in their working places, at the chemical industry or in the crop fields. Here, we present a brief review of biomonitoring studies carried out in people occupationally exposed to pesticides and that use MN in lymphocytes or buccal cells as a target to determine the induction of genotoxic damage. Thus, people working in the chemical industry producing pesticides, people spraying pesticides and people dedicated to floriculture or agricultural works in general are the subject of specific sections. MN is a valuable genotoxic end point when clear exposure conditions exist like in pesticide production workers; nevertheless, better study designs are needed to overcome the uncertainty in exposure, genetic susceptibility and statistical power in the studies of sprayers and floriculture or agricultural workers.

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