[Cross-resistance of HO-221 and various antitumor agents in sublines of mouse leukemia].
HO-221, N-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2- nitrobenzoyl) urea is a new benzoylphenylurea derivative. The compound exhibits significant antitumor effects against various animal tumors, and was especially effective against the solid tumors implanted subcutaneously. HO-221 inhibits DNA polymerase alpha activity strongly in vitro. In this study, we examined the cross-resistance of HO-221 to various antitumor agents using sublines of mouse leukemia. HO-221 showed antitumor effects in mice bearing L 1210 or P 388 leukemia resistant to 10 antitumor agents, DM (daunomycin), MMC (mitomycin C), CDDP (cisplatin), 5-FU (5-fluorouracil), Ara-C (cytosine arabinoside), MTX (methotrexate), CPA (cyclophosphamide), CQ (carboquone), ADM (adriamycin) and VCR (vincristine), respectively. These antitumor agents were also effective in P 388 leukemia resistant to HO-221 (P 388/HO-221). Furthermore, CDDP- and MMC-resistant sublines showed a collateral sensitivity to HO-221 in vivo. The grow the inhibitory effects were also noted in vitro in ADM-, CDDP- and MMC-resistant cells by HO-221. However, the in vitro experiments didn't show such collateral sensitivity on the resistant sublines. These results suggest that there is no cross-resistance between HO-221 and other known antitumor agents, and that HO-221 seemed to be worth for evaluating clinical usefulness.
Nakajima
T
T
Research Division, Green Cross Corporation, Osaka, Japan.
Masuda
H
H
Okamoto
T
T
Watanabe
M
M
Yokoyama
K
K
Yamada
N
N
Fujimoto
S
S
Tsukagoshi
S
S
Taguchi
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology; D007941:Leukemia P388 / Q000188:drug therapy / Q000473:pathology; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D001549:Benzamides; D008937:Mitomycins; D009578:Nitrobenzenes; C066688:N-(4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl)-N'-(2-nitrobenzoyl)urea; D016685:Mitomycin; D004317:Doxorubicin; D002945:Cisplatin