実験的膀胱腫瘍モデルを用いた抗癌剤効果判定

Abstract

N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)を8週間投与するラット膀胱腫瘍実験モデルを用いて抗癌剤の効果判定を行った.1)抗癌剤単剤投与実験では, 5-FU, FT-207, CQ, VCRおよびCDDPの投与群において膀胱腫瘍の発生頻度が抑制され, ADM, MMC, CPM, NCSおよびBLM投与の各群では抑制されなかった.2)抗癌剤の経口投与実験において, 5-Fu関連物質は膀胱腫瘍発生の抑制がみられ, とくにUracil, 1-Hexylcarbamoyl-5-fluorouracil投与群では用量依存的に膀胱腫瘍発生の抑制がみられた

The chemotherapeutic agents were evaluated using the experimental urinary bladder tumor rat model induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Nine hundred and fourteen male rats received 0.05% BBN in drinking water for 8 weeks, and were divided into 35 groups to follow the regimens of chemotherapeutic agents. Thirty one groups received the agents after BBN treatment, and 4 groups were given the oral agents starting simultaneously with BBN treatment. All rats were killed at 20 weeks and incidence of the urinary bladder was examined histopathologically. The following 13 agents were evaluated; adriamycin (ADM), mitomycin-C (MMC), cyclophosphamide (CPM), 5-fluoro-uracil (5-Fu), N-(2-tetrahydrofuryl)-5-fluorouracil (FT-207), neocarcinostatine (NCS), carbazil quinone (CQ), bleomycin (BLM), vincristine (VCR) and cis-diammine-dichloroplatinum (CDDP) were dosed intraperitoneally, and N-(2-tetrahydrofuryl)-5-fluorouracil (FT-207), 1: 4 mixture of FT-207 and uracil (UFT) and 1-Hexylcarbamoyl-5-fluorouracil (HCFU) were dosed orally. Among these agents, 5-Fu, FT-207, CQ, VCR, CDDP, UFT and HCFU were effective in inhibiting the incidence of urinary bladder tumor induced by BBN. In conclusion, the experimental bladder tumor rat model induced by BBN seems to be useful in evaluating the effective chemotherapeutic agents for a superficial bladder cancer. The importance of the experimental animal model for the evaluation of chemotherapeutic agents is discussed.