D'Incalci M, Taverna P, Erba E, Filippeschi S, Potenza D, Mariani L, Citti L, Catapano C V
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Anticancer Res. 1991 Jan-Feb;11(1):115-21.
Using L1210 and a subline resistance to chloroethylnitrosoureas (L1210/BCNU), we found that the resistance to 1-(2-chloroethyl)-1-nitrosourea (CNU) or to diethyl-1-3-(2-chloroethyl)-3-nitrosoureido ethyl phosphonate (fotemustine) can be reversed by a pretreatment with O6-methyl Guanine (O6-mGua) or temozolomide. In L1210/BCNU but not in L1210 the pretreatment with O6mGua caused an increased peak level of CNU-induced DNA-interstrand crosslinks. We then evaluated whether the resistance to BCNU could be counteracted in vivo by i.p. O6mGua treatment of L1210/BCNU bearing mice. The results were negative due to the fact that O6mGua, which was not toxic when given alone, caused a high toxicity when associated with BCNU.
使用L1210及其对氯乙基亚硝基脲耐药的亚系（L1210/BCNU），我们发现用O6-甲基鸟嘌呤（O6-mGua）或替莫唑胺预处理可逆转对1-(2-氯乙基)-1-亚硝基脲（CNU）或二乙基-1-3-(2-氯乙基)-3-亚硝基脲基乙基膦酸酯（福莫司汀）的耐药性。在L1210/BCNU中，而非L1210中，用O6mGua预处理会导致CNU诱导的DNA链间交联峰值水平升高。然后我们评估了对BCNU的耐药性在体内是否可以通过对携带L1210/BCNU的小鼠腹腔注射O6mGua来抵消。结果是否定的，因为单独给药时无毒的O6mGua与BCNU联合使用时会产生高毒性。
