Chapter 2.4 - Effects of Environmental Factors on DNA: Damage and Mutations

Abstract

Chemicals in the environment pose myriad challenges to organisms, principally via toxicity or mutagenesis. Mutations are the result of changes in the DNA base sequence or the chemical addition of adducts onto the bases, which prevent correct DNA replication and/or transcription of the DNA into RNA. Additionally, spontaneous mutation of DNA bases can also occur by tautomerization, base deletions or additions, deamination, etc. Every human cell experiences about 10,000 “insults” every day, most of which are repaired by one of the multiple DNA repair systems of the cell. DNA replication itself results in a few base changes every cycle. Io protect itself from accumulating mutations, cells typically divide (mitosis) between 40 and 70 times (the so-called Hayflick number) before they undergo programmed cell death (apoptosis). Hence, it is the accumulation of mutations in the DNA due to chemicals in the environment that seems to be a causative agent of maladies, including cancer. (It is currently hypothesized that multiple DNA base changes, DNA rearrangements, etc., are necessary for the induction of cancer, which is uncontrolled and unregulated cell growth and division). Environmental chemicals that are linked to DNA damage include (but are not limited to) alkylating agents, Agent Orange, intercalating agents, dichlorodiphenyltrichloroethane, triclosan, and plasticizers (including polyvinyl chloride, phthalates, and bisphenol A and its derivatives). Some of the environmental chemicals may not cause DNA damage directly; they can cause epigenetic changes. This means that the DNA base sequence is not altered but the base is chemically modified so that the genetic information is expressed in a manner abnormal to correct cellular function. Moreover, it has become evident that posttranslational modifications of proteins associated with DNA (e.g., histones) can also lead to mutation via incorrect regulation of gene expression. Results of contemporary studies on animals (including human) have also indicated that epigenetic changes can occur in response to environmental distress (e.g., famine, toxic chemicals) and cause an ailment(s) in the individual due to altered gene expression, and that these epigenetic changes, altered gene expression, and ailment(s) are passed on to at least two and maybe three generations of offspring. The gene sequence, however, remains unchanged! This is referred to as transgenerational inheritance.