Table 1.

Summary of studies investigating the effects of toxicants on mtDNA mutagenesis.

	Toxicant	Lesion	Mutation	System	Method	Reference
Laboratory studies	B[a]P 7,8-diol 9,10-epoxide	dG-N2-deoxyguanosine	G → T, mtDNA deletions, decrease mtDNA CN	Biochemical	Oligonucleotide substrates	Graziewicz et al. (2004)[133]
	B[a]P; N-ethyl-N-nitrosourea (ENU)	dG-N2-deoxyguanosine; alkylation	None	M. musculus; bone marrow and liver	RMC; 12S rRNA and ND5 sequencing	Valente et al. (2016)[134]
	Methyl methanesulfonate (MMS)	Alkylation	C → G	S. cerevisiae	16S rRNA sequencing	Stumpf and Copeland (2014) [135]
	Nucleoside reverse transcriptase inhibitors (NRTIs)	Nucleotide analog misincorporation	mtDNA depletion	-	-	Young (2017) [136]
	Cadmium Chloride	Unknown; hypothesize oxidative stress	Accumulation of common mtDNA deletion	Rat; renal cortex	PCR	Takaki et al. (2004) [137]
Epidemiological studies	Lead	Unknown; hypothesize oxidative stress	Increased incidence of transition mutations (T:A → C:G)	Blood from male workers	Whole genome sequencing	Mani et al. (2020) [138]
	Pesticides	Unknown; mixture	Inadequate statistical power	Blood and lung tissue from farmers	Whole genome sequencing	Wang and Zhao (2012) [139]
	Ultraviolet C	Pyrimidine dimers	Clonal expansion of common mtDNA deletion	Skin tissue from patients	Amplicon sequencing	Birket and Birch-Machin (2007) [140]
	Smoking, NRTIs, age	Not measured; bulky adducts, ROS, POLG inhibition	Age: T:A → C:G; smoking: ↑ heteroplasmy (clonal expansion)	Blood from smoking and non-smoking females, HIV+ patients	D-loop	Ziada et al. (2019) [141]
Population genetics	Radiation	Break or oxidative damage	Increased haplotype diversity	Chernobyl bank vole	Whole genome sequencing	Kesäniemi et al. (2020) [142], Baker et al. (2017) [143]
	Industrial pollution (heavy metals, PAHs)	Unknown; mixture	Reduced haplotype diversity	Azerbaijan marsh frog	CYTB, D-loop	Matson et al. (2006) [144]