8-Hydroxyguanine, a DNA adduct formed by oxygen radicals: its implication on oxygen radical-involved mutagenesis/carcinogenesis.
Oxygen radicals have been suggested to be involved in mutation/carcinogenesis. The C-8 position of guanine residues in DNA is hydroxylated to produce 8-hydroxyguanine (8-OH-Gua) in DNA in vitro by various oxygen radical producing agents. The formation of 8-OH-Gua was also observed in cellular DNA in vivo by radiation or oxygen radical forming carcinogens. The 8-OH-Gua residue in DNA is often misread in the position of 8-OH-Gua residue itself but also at neighboring residues next to 8-OH-Gua. When second guanine in codon 12 was specifically replaced with 8-OH-Gua and transferred to NIH3T3, the recipient cells were transformed to malignant cell type. E. coli was found to contain an endonuclease which specifically recognizes 8-OH-Gua residue and cleave DNA strand before and after the modified base. The data obtained imply that 8-OH-Gua formed in DNA in vivo is recognized as an abnormal modified base which, if not repaired, play a role in the mediation of oxygen radical-involved mutation/carcinogenesis.
Kasai
H
H
Biology division, National Cancer Center Research Institute, Tokyo, Japan.
Chung
M H
MH
Jones
D S
DS
Inoue
H
H
Ishikawa
H
H
Kamiya
H
H
Ohtsuka
E
E
Nishimura
S
S
D000818:Animals; D001483:Base Sequence; D002273:Carcinogens; D004249:DNA Damage; D004720:Endonucleases / Q000378:metabolism; D005609:Free Radicals; D011905:Genes, ras / Q000235:genetics; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009153:Mutagens; D010100:Oxygen / Q000737:chemistry / Q000633:toxicity*; D014170:Transformation, Genetic
D002273:Carcinogens; D005609:Free Radicals; D009153:Mutagens; C024829:8-hydroxyguanine; D006147:Guanine; D004720:Endonucleases; D010100:Oxygen