Marks T A, Venditti J M
Cancer Res. 1976 Feb;36(2 Pt 1):496-504.
Several antitumor agents known to bind DNA were complexed with this macromolecule and tested for activity against experimental animal tumor systems. Combination studies with these agents and DNA were carried out at the same time. Actinomycin D activity against the P388 lymphocytic leukemia in BALB/c X DBA/2 F1 mice was significantly potentiated by calf thymus DNA, both when complexed and when injected in combination. The DNA could be given as much as 4 hr before or after the antibiotic and still give potentiation. Synergism was also obtained when the DNA was autoclaved prior to complexing and/or injecting. Similarly, adriamycin activity against the L1210 lymphoid leukemia in DBA/2 mice was significantly potentiated by autoclaved herring sperm DNA, both as a complex and when injected in combination. When above-optimal levels of adriamycin were complexed with autoclaved herring sperm DNA and injected into BALB/c mice inoculated with the Madison 109 alveogenic carcinoma, the early lethality was delayed and antitumor activity was sometimes observed. Herring sperm DNA injected alone also had antitumor activity against the Madison 109 tumor. Similarly, activity was obtained against this tumor system with calf thymus DNA and actinomycin D when injected alone. In addition, DNA, in combination and when complexed with actinomycin, prevented the toxicity observed with BALB/c mice, inoculated with the Madison 109 tumor, were given injections of an above-optimal dose of this antibiotic.
已知几种能与DNA结合的抗肿瘤药物与这种大分子形成复合物，并对实验动物肿瘤系统进行活性测试。同时开展了这些药物与DNA的联合研究。在BALB/c×DBA/2 F1小鼠中，无论是形成复合物时还是联合注射时，小牛胸腺DNA都能显著增强放线菌素D对P388淋巴细胞白血病的活性。DNA可在抗生素给药前或给药后4小时给予，仍能产生增强作用。当DNA在形成复合物和/或注射前进行高压灭菌时，也能获得协同作用。同样，在DBA/2小鼠中，无论是作为复合物还是联合注射时，经高压灭菌的鲱鱼精DNA都能显著增强阿霉素对L1210淋巴白血病的活性。当将高于最佳剂量的阿霉素与经高压灭菌的鲱鱼精DNA形成复合物并注射到接种了麦迪逊109肺泡癌的BALB/c小鼠体内时，早期致死率延迟，有时还能观察到抗肿瘤活性。单独注射鲱鱼精DNA对麦迪逊109肿瘤也有抗肿瘤活性。同样，单独注射小牛胸腺DNA和放线菌素D时，对该肿瘤系统也有活性。此外，当DNA与放线菌素联合并形成复合物时，可防止给接种了麦迪逊109肿瘤的BALB/c小鼠注射高于最佳剂量的这种抗生素时所观察到的毒性。
