Formation of DNA adducts and tumor growth delay following intratumoral administration of DTI-015.
Formation of DNA adducts and tumor growth delay following intratumoral administration of DTI-015.
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瘤内施用 DTI-015 后 DNA 加合物的形成和肿瘤生长延迟。
DOI：
10.1023/a:1023383717833
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发表时间：
2003
影响因子：
3.9
通讯作者：
Levin,VictorA
中科院分区：
文献类型：
--
作者：
Bodell,WilliamJ;Giannini,DonaldD;Singh,Saira;Pietronigro,Dennis;Levin,VictorA
DTI-015 （BCNU， 100%乙醇）瘤内给药利用溶剂促进灌注治疗肿瘤。RIF-1肿瘤采用单独注射乙醇或0.05-1.0 mg DTI-015或静脉注射0.5 mg BCNU治疗。单独使用乙醇或静脉注射0.5 mg BCNU不会产生明显的生长延迟。相比之下，DTI-015的IT管理在每个治疗剂量下都产生了显著的生长延迟（p< 0.05 top< 0.001）。我们量化了N7-（2-羟乙基）鸟嘌呤（N7- hoetg）在用0.5 mg DTI-015或0.5 mg BCNU治疗24小时后在RIF-1肿瘤中的水平。N7-HOEtG （μmol/mol DNA）水平在未治疗组和BCNU治疗组≤0.08，在DTI-015治疗组为13.1±5.6。给药DTI-015后，在RIF-1肿瘤中检测到的N7-HOEtG水平比BCNU治疗的肿瘤样品中检测到的N7-HOEtG水平高164倍。这些研究表明，与系统给药相同剂量的BCNU相比，IT给药DTI-015在肿瘤中产生高水平的DNA加合物，这对应于肿瘤生长延迟的显着增加。
Intratumoral (IT) administration of DTI-015 (BCNU in 100% ethanol) utilizes solvent facilitated perfusion for the treatment of tumors. RIF-1 tumors were treated by IT injection of either ethanol alone or 0.05–1.0 mg of DTI-015 or by iv injection of 0.5 mg of BCNU. Treatment with ethanol alone or iv injection of 0.5 mg of BCNU did not produce a significant growth delay. In contrast, IT administration of DTI-015 produced a significant growth delay at each of the treatment doses (p< 0.05 top< 0.001). We have quantified the levels of N7-(2-hydroxyethyl) guanine (N7-HOEtG) in RIF-1 tumors 24 h following either IT treatment with 0.5 mg DTI-015 or ip administration of 0.5 mg BCNU. Levels of N7-HOEtG (μmol/mol DNA) were ≤0.08 for both untreated controls and following ip treatment with BCNU and 13.1 ± 5.6 following IT administration of DTI-015. The levels of N7-HOEtG detected in RIF-1 tumors following IT administration of DTI-015 were 164-fold higher than the level(s) of N7-HOEtG in the ip BCNU treated tumor samples. These studies demonstrate that IT administration of DTI-015 produces high levels of DNA adducts in the tumor which correspond to a significant increase in tumor growth delay compared to the same dose of BCNU administered systemically.