[Depletion of O6-alkylguanine alkyltransferase and chromosome damage induced by cisplatin, ning xin platin and carboplatin].
O6-Alkylguanine-DNA-alkyltransferase (O6-AGT) is a very important DNA repair protein known to carry out the transfer of alkyl groups from the O6 position of guanine in alkylated DNA to a cysteine acceptor site contained within its own protein sequence. In this work, the activity of O6-AGT in different cell lines and the relationship between the depletion of the enzyme and the frequency of micronuclei induced by cisplatin (DDP), Ning Xin platin (camphoramine chloroacetic platinum, CCP) or carboplatin (JM-8) in KB and CHL cells were studied. Experiments indicate that KB cells showed higher O6-AGT activity (greater than 400 dpm/300 micrograms protein extracts) which belonged to Mer+ cells, but CHL, HL-60 and L1210 cells showed very low O6-AGT activity (less than 50 dpm/300 micrograms protein extracts) which can be considered to be Mer- cells. Cytotoxicity studies indicated that no mer- selection was observed in these platinum complexes for KB, HL-60, CHL and L1210 cells. However, a good relationship between the depletion of O6-AGT and the frequency of micronuclei induced by the platinum complexes was obtained. CCP caused the highest depletion of the enzyme and exhibited highest potency in damaging chromosome.
Wang
L G
LG
Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing.
Liu
X M
XM
Fan
P D
PD
Ji
X J
XJ
D000818:Animals; D016190:Carboplatin / Q000633:toxicity*; D002875:Chromosomes / Q000187:drug effects*; D002945:Cisplatin / Q000633:toxicity*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007624:KB Cells / Q000187:drug effects / Q000201:enzymology; D007939:Leukemia L1210 / Q000235:genetics / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology; D008780:Methyltransferases / Q000378:metabolism*; D015162:Micronucleus Tests; D019853:O(6)-Methylguanine-DNA Methyltransferase; D009944:Organoplatinum Compounds / Q000633:toxicity*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D009944:Organoplatinum Compounds; C053095:camphoramine chloroacetic platinum; D016190:Carboplatin; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D002945:Cisplatin