Characterization of naturally acquired multiple-drug resistance of Yoshida rat ascites hepatoma AH66 cell line.
Characteristics of multiple-drug resistance of rat ascites hepatoma AH66, a cell line induced by dimethylaminoazobenzene and established as a transplantable tumor, were compared with those of AH66F, a drug sensitive line obtained from AH66. The AH66 cell line was resistant to vinblastine, adriamycin, SN-38 an active form of camptothesine, etoposide, and clorambucil by 10-fold or more than the AH66F cell line. The resistance of AH66 cells to vinblastine, adriamycin, and SN-38 was closely related to P-glycoprotein overexpression in the plasma membrane, because the resistance was significantly inhibited by verapamil. AH66 cells contained much glutahione and had a high activity of glutathione S-transferase P-form (GST-P), compared with AH66F cells, and resistance to clorambucil was decreased by treatment with buthionine sulfoximine, an inhibitor of glutathione synthesis. AH66 cells have a similar topoisomerase I activity, but about 6 times lower topoisomerase II activity than AH66F cells. Therefore, the resistance to etoposide and a part of the resistance to adriamycin of AH66 cells seems to depend upon this low topoisomerase II activity. These results, show that the AH66 cell line has high multiple-drug resistance compared with the AH66F cell line, by several mechanisms. Consequently, the AH66 and AH66F cell lines are useful to study naturally acquired multiple-drug resistance of hepatomas.
Miyamoto
K
K
Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Wakabayashi
D
D
Minamino
T
T
Nomura
M
M
Wakusawa
S
S
Nakamura
S
S
D000818:Animals; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
D008668:Metallothionein; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II