Folate and Colorectal Cancer in Rodents: A Model of DNA Repair Deficiency

Table 1

Genome instability phenotypes in base excision repair mutant models.

Gene	Genotype	Phenotype	Genome instability
UNG; [27–29]	Ung^−/−	Viable; B-cell lymphoma; Neuronal sensitivity to oxidative damage; Neurodegeneration	Uracil accumulation in brain
SMUG; [30, 31]	Smug^tg/+; Smug^/siRNAUng^−/−	Viable	C to T mutagenesis
OGG1; [32–35]	Ogg1^−/−	Viable; UVB-induced skin tumors	8-OHdG accumulation; G to T mutagenesis; Gamma radiation-induced DSB in OGG1 overexpressing cells
MYH; [36, 37]	Myh^−/−; Ogg1^−/−Myh^−/−	Viable; Reduced survival; Lung, ovarian, and lymphoid tumors	Spontaneous mutagenesis; G to T mutagenesis
AAG; [38–40]	Aag^−/−	Viable; Sensitivity to alkylation damage; Retinal degeneration in +/−	Increased mutagenesis
NTH
[41, 42]; [35, 43]	Nth1^−/−; Ogg1^−/−Nth^−/− TK6; cell line	Viable	Increased thymine glycol in liver after X-ray irradiation
[44]	Ogg1^−/−Nth^−/− mice	Viable	Gamma irradiation-induced DSB; H2O2 resistant
TDG; [45]	Tdg^−/−	Embryonic lethal	Deficient repair of mtDNA
MBD4; [46, 47]	Mbd4^−/−; Mbd4^−/−Apc^min/+	Viable; Intestinal adenomas	Aberrant chromatin metabolism; C to T mutagenesis
FEN; [48, 49]	Fen1^−/−; Fen^+/−Apc^1638N	Early embryonic lethal; Intestinal adenocarcinoma; Decreased survival	Microsatellite instability; Extensive apoptosis
APE; [50, 51]; [20]	Ape^−/−; Ape^+/−	Embryonic lethal; Sensitive to oxidative stress
[52]	Apex1^+/−XPC^−/−	Increased UV-induced skin cancer	Increased mutagenicity; Papillary adenocarcinoma and lymphoma
XRCC; [53, 54]	Xrcc1^−/−	Embryonic lethal
[55, 56]	Xrcc1^+/−	Increased AOM-induced ACF	SCE in embryo and cell lines
β -Pol; [21, 64]	β-Pol^−/−	Embryonic lethal	DSB accumulation; Increased mutagenesis
[57–60]	β-Pol^+/−	Viable; Accelerated aging; Lymphoma and adenocarcinomas	Increased SCE in MEFs; SSB accumulation
LIGI; [61]	Lig^−/−	Embryonic lethal defective erythropoiesis	Oxidative stress sensitivity; Increased mutagenesis; Chromosomal aberrations
LIGII; [62]	Lig^−/−	Embryonic lethal	Elevated SCE