DNA repair enzymes (ATSDR, 2023b; Cam- eron et al., 2011; Chen et al., 2010; Chiocca et al., 1991; Clemens et al., 2005; Cohen et al., 1993; Haugen et al., 1994; Klein et al., 1994; Salnikow et al., 2003). In stark contrast are the genotoxic eects of Zn. In fact, there is an association between Zn deficiency and carcinogenicity. Genotox- icity studies failed to provide evidence for mutagenicity of Zn, but there are indications of weak clastogenic eects. Although chro- mosome aberrations have been observed in the lymphocytes of workers at a Zn smelting plant, those workers had elevated levels of Pb and cadmium (Bauchinger et al., 1976). Interestingly, in many cases, exposure to mixtures of these metals and the resulting genotoxic eects can dier from the eects of exposure to a single metal. Welding, for example, can generate a complex mixture of genotoxic metals (e.g., Cr, Ni) that might result in altered DNA methylation, telomere length, and shelterin proteins; DNA damage; and DNA strand breaks (Shoeb, Kodali, Far-
TABLE 1
Genotoxic Endpoints and Definitions
Endpoint
Definition
Chromosomal damage
Chromosomal alterations (i.e., coding properties) that occur during division of cells
DNA methylation
Addition of methyl group to cytosine (5’-CpG-3’)
DNA–protein cross-linking
Chemically activated trapping of proteins on DNA strands
Micronuclei formation Fragments of chromosomal matter outside the nucleus Sister-chromatid exchange Exchange of genetic material between two identical copies of the same chromosome DNA repair inhibition Inhibition of the natural process of repairing a harmful DNA lesion Gene mutation Alteration of DNA or nucleotide sequence of one or more genes Chromosomal aberrations Changes in chromosome number or structure DNA fragmentation Rapid separation or breaking of DNA strands into pieces DNA strand breaks Single- or double-break of the DNA sequence in the genetic material Telomere alteration Change in the noncoding ends of the DNA that serves to protect the coding portion
Note. Endpoints are listed in hierarchical order from less to more permanent gene damage.
TABLE 2
Genotoxic Endpoints for Six Metals
Chromium-6 (Cr 6+)
Arsenic (As)
Nickel (Ni)
Lead (Pb)
Mercury (Hg)
Zinc (Zn)
National Toxicology Program classification Substance Priority List rank
1
1
1 (Ni compounds)
2
3
3
17
1
58
2
3
75
Chromosomal damage
* *
DNA methylation
DNA–protein cross-linking Micronuclei formation Sister-chromatid exchange DNA repair inhibition Gene mutation Chromosomal aberrations
*
* * * *
DNA fragmentation DNA strand breaks Telomere alteration
* Represents some studies with preventive effects. Note. Table 1 presents the number of published studies that identified the genotoxic endpoint from a search of toxicological profiles and literature using PubMed conducted on October 17, 2022. Search terms included: endpoint induced by X metal exposure (e.g., telomere alteration induced by arsenic metal exposure, only lead and zinc were searched as Pb and Zn). The shading is based on the number of given genotoxic endpoints studied: green = 1–10; yellow = 11–24; and red = >24. A lack of shading indicates no studies were found. For the National Toxicology Program classification: 1 = known carcinogen; 2 = reasonably anticipated to be a human carcinogen; and 3 = not classified by the National Toxicology Program. For the Substance Priority List rank: 1 represents the highest priority. The only form of chromium classified as carcinogenic to humans is hexavalent chromium (Cr 6+ ). Source: Agency for Toxic Substances and Disease Registry, 2005, 2007, 2012, 2020, 2022c, 2023b.
31
December 2023 • Journal of Environmental Health
Powered by FlippingBook