Rizvi R Y, Rahman A, Hadi S M
Biosci Rep. 1986 Jun;6(6):557-64. doi: 10.1007/BF01114952.
S1 nuclease hydrolysis and hydroxyapatite chromatography were used to study the effect of the alkylating antibiotic, streptozotocin, on the secondary structure of DNA. Native calf thymus DNA was alkylated in vitro with increasing concentrations of streptozotocin and subjected to S1 nuclease hydrolysis. An increasing degree of DNA degradation was seen, suggesting a destabilization of the secondary structure. Indirect evidence, deduced from alkaline hydrolysis, effect of NaCl on S1 nuclease hydrolysis, and hydroxyapatite chromatographic analysis of alkylated DNA, suggested a significant alkylation of DNA phosphates in addition to DNA bases. Nicotinamide has been reported to alter the cytotoxic and carcinogenic effects of streptozotocin. Our experiments indicate that in the presence of nicotinamide, streptozotocin causes the formation of a greater proportion of alkylated bases in relation to alkyl phosphotriesters. This may have significance in relation to the differential cytotoxicity of streptozotocin in the absence and presence of nicotinamide.
用S1核酸酶水解和羟基磷灰石层析法研究了烷基化抗生素链脲佐菌素对DNA二级结构的影响。用浓度递增的链脲佐菌素在体外对天然小牛胸腺DNA进行烷基化处理，然后进行S1核酸酶水解。观察到DNA降解程度增加，这表明二级结构不稳定。从碱性水解、NaCl对S1核酸酶水解的影响以及对烷基化DNA的羟基磷灰石层析分析推断出的间接证据表明，除了DNA碱基外，DNA磷酸也发生了显著的烷基化。据报道，烟酰胺可改变链脲佐菌素的细胞毒性和致癌作用。我们的实验表明，在烟酰胺存在的情况下，与烷基磷酸三酯相比，链脲佐菌素导致形成更大比例的烷基化碱基。这可能与烟酰胺存在与否时链脲佐菌素的不同细胞毒性有关。
