Ashby J, Vogel E W, Tinwell H, Callander R D, Shuker D E
ICI Central Toxicological Laboratory, Macclesfield, Ches., UK.
Mutat Res. 1993 Mar;286(1):101-9. doi: 10.1016/0027-5107(93)90005-z.
The antineoplastic agent fotemustine is shown to be a base-pair mutagen to Salmonella. Activity is more marked in the uvrB-proficient strain G46 than in the repair-deficient strain TA1535. This is consistent with its ability to cross-link DNA. Potent activity as a somatic and germ-cell mutagen to Drosophila was also observed. A potent clastogenic response was given by fotemustine in the mouse bone marrow following either oral gavage or intraperitoneal injection of a single dose of 5 mg/kg. In each of these respects it is shown to be indistinguishable from the structurally related antineoplastic agent and human carcinogen MeCCNU. It is concluded that fotemustine should be regarded as having clear potential to induce cancer in humans. Based on these data, including the preponderance of chromosome breakages over recessive lethal mutations in Drosophila, an estimated rodent carcinogenic potency (TD50) of between 15-150 mg/kg is suggested for fotemustine.
抗肿瘤药物福莫司汀对沙门氏菌具有碱基对诱变作用。在uvrB功能正常的菌株G46中的活性比修复缺陷型菌株TA1535中更明显。这与其交联DNA的能力一致。还观察到福莫司汀对果蝇具有强大的体细胞和生殖细胞诱变活性。在经口灌胃或腹腔注射单剂量5mg/kg后，福莫司汀在小鼠骨髓中引发了强烈的致染色体断裂反应。在上述各方面，它与结构相关的抗肿瘤药物及人类致癌物甲基CCNU并无差异。得出的结论是，福莫司汀应被视为具有明确的诱发人类癌症的潜力。基于这些数据，包括果蝇中染色体断裂比隐性致死突变更为普遍，建议福莫司汀的啮齿动物致癌效力（TD50）在15 - 150mg/kg之间。
