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Review
. 2018 Oct 1;165(2):272-276.
doi: 10.1093/toxsci/kfy184.

The Evolution of Carcinogenesis

Jeffrey M Peters  1 , Frank J Gonzalez  2
Affiliations
Review

The Evolution of Carcinogenesis

Jeffrey M Peters et al. Toxicol Sci. .
No abstract available

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Mechanisms by which environmental chemicals interact with chemical metabolism and endogenous signaling. A, Environmental chemical exposure can be metabolized by xenobiotic metabolizing enzymes to reactive intermediates that form adducts with DNA, and if not repaired by DNA repair enzymes, cause permanent mutations in critical genes that are known to be targeted by some chemicals. This results in the formation of precancerous cells. Under normal situations, there are molecular pathways that regulate cell proliferation and apoptosis that can cause these mutant cells to stop growing or undergo apoptosis, thereby preventing the formation of a tumor. B, Environmental chemical exposure can be metabolized by xenobiotic-metabolizing enzymes to reactive intermediates that form adducts with DNA, and if not repaired by DNA repair enzymes, cause permanent mutations in critical genes that are known to be targeted by some chemicals, such as tumor suppressors or proto-oncogenes. This metabolism can be influenced by polymorphisms in the xenobiotic metabolizing enzymes that catalyze these reactions. Collectively, the pathway outlined in (B) results in the formation of precancerous cells. If the environmental chemical(s) interfere with normal signaling such as those that prevent proliferation or induce apoptosis, and this can lead to the formation of tumors and cancer.
Figure 2.
Figure 2.
Mechanisms by which environmental chemicals interact with genes and cause cancer. A, Environmental chemical exposure can be metabolized by xenobiotic metabolizing enzymes to reactive intermediates that form adducts with DNA, and if not repaired by DNA repair enzymes, cause permanent mutations in critical genes that are known to be targeted by some chemicals, such as tumor suppressors or proto-oncogenes. This metabolism can be influenced by polymorphisms in the xenobiotic metabolizing enzymes that catalyze these reactions. This results in the formation of precancerous cells. Environmental chemical(s) may also cause mutagenesis via xenobiotic metabolizing enzymes forming reactive intermediates that form adducts with genes encoding normal signaling that prevents proliferation or induction of apoptosis (??) and combined this can lead to the formation of tumors and cancer. B, Environmental chemical(s) may cause mutagenesis via xenobiotic metabolizing enzymes forming reactive intermediates that form adducts with genes encoding normal signaling proteins that prevents proliferation or induction of apoptosis (??). “Normal” endogenous signaling may result in the generation of reactive intermediates (or reactive oxygen species) that can cause mutations in genes that are critical for tumor suppression or oncogenes that combined with the former alterations, leads to formation of tumors and cancer. There are many combinations of the pathways outlined in Figures 1 and 2 that could theoretically participate in the etiology of how chemicals, genes and endogenous signaling interact to cause cancer. Moreover, the regulation of each of the critical steps in these pathways can also be central and possibly targeted to prevent or treat different cancers.
See this image and copyright information in PMC

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