The Mutagenic Impact of Environmental Exposures in Human Cells and Cancer: Imprints Through Time

Abstract

During life, the DNA of our cells is continuously exposed to external damaging processes. Despite the activity of various repair mechanisms, DNA damage eventually results in the accumulation of mutations in the genomes of our cells. Oncogenic mutations are at the root of carcinogenesis, and carcinogenic agents are often highly mutagenic. Over the past decade, whole genome sequencing data of healthy and tumor tissues have revealed how cells in our body gradually accumulate mutations because of exposure to various mutagenic processes. Dissection of mutation profiles based on the type and context specificities of the altered bases has revealed a variety of signatures that reflect past exposure to environmental mutagens, ranging from chemotherapeutic drugs to genotoxic gut bacteria. In this review, we discuss the latest knowledge on somatic mutation accumulation in human cells, and how environmental mutagenic factors further shape the mutation landscapes of tissues. In addition, not all carcinogenic agents induce mutations, which may point to alternative tumor-promoting mechanisms, such as altered clonal selection dynamics. In short, we provide an overview of how environmental factors induce mutations in the DNA of our healthy cells and how this contributes to carcinogenesis. A better understanding of how environmental mutagens shape the genomes of our cells can help to identify potential preventable causes of cancer.

Risk Factors for Medication-Related Osteonecrosis of the Jaw—A Binomial Analysis of Data of Cancer Patients from Craiova and Constanta Treated with Zoledronic Acid

“…Like the study by Marciano et al conducted in an Italian population [27], the current study presents a descriptive statistical analysis of a part of a Romanian cancer population from two geographical regions who were treated with zoledronic acid, as well as the results of the binomial logistic regression analysis through which several risk factors were associated with the occurrence of MRONJ. As some researchers have pointed out [32], the geographical origin of the population studied is important since genetic and environmental factors could be different [40][41][42]. Our study groups belong to two different geographical regions of the country situated 450 kilometers apart, one with a sea-side opening (Dobrogea, with its municipality in Constanta, South-East Romania), and the other, in the plain area close to Bulgaria (Oltenia, with its municipality in Craiova, South-West Romania).…”

Phenotypical mapping of TP53 unique missense mutations spectrum in human cancers

“…Excluding the amino acid Tyr103, all the residues in the DNA binding domain are reported to be mutated in cancer (Figure 3a) . The majority of the p53 hotspot mutants are reported in the DNA binding domain due to their presence in the methylated CpG dinucleotides island which is prone to spontaneous mutation by certain environmental carcinogens [35], such as polycyclic aromatic hydrocarbons in tobacco, which preferentially binds to guanines in methylated CpG sites [36,37], and UV irradiation often modifies methylated cytosines [21]. To assess the propensity of mutation in each amino acid residue in the DNA binding domain we divided the residues based on their location in the domain such as the DNA contact region, Zinc binding region and conformational mutants that lead to the loss of thermostability of p53 (Figure 4a-c) .…”

Congenital Heart Disease and the Risk of Cancer: An Update on the Genetic Etiology, Radiation Exposure Damage, and Future Research Strategies

“…The joint effect can be summarized in the following sentence: “genetics loads the gun and the radiation pulls the trigger”. However, it is likely that other environmental exposures (e.g., pollution, endocrine-disrupting chemicals) beyond ionizing radiation may be related to both CHD and cancer late in life [ 55 , 56 ].…”