Bertini R, Coccia P, Pagani P, Marinello C, Salmona M, D'Incalci M
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Carcinogenesis. 1990 Jan;11(1):181-3. doi: 10.1093/carcin/11.1.181.
We investigated whether treatment with the interferon inducer polyinosinic-polycytidylic acid and other cytokines (interleukin-1, tumor necrosis factor) or the cytokine inducer lipopolysaccharide modified O6-alkylguanine-DNA alkyltransferase (AT) in rat liver. AT levels were determined in liver extracts using N-[3H]methyl-N-nitrosourea alkylated calf thymus DNA as substrate and an HPLC procedure to measure O6-methylguanine. Doses as low as 0.1 mg/kg i.p. of polyinosinic-polycytidylic acid caused a highly significant increase (P less than 0.01) in AT levels in the liver, evident either 24 or 48 h after treatment. Lipopolysaccharide at the dose of 80 micrograms/kg i.p. also induced AT whereas interleukin-1 (60 micrograms/kg) or tumor necrosis factor (60 micrograms/kg) were inactive. Treatment with human recombinant interferon alpha A/D caused a highly significant increase in AT levels, thus confirming the hypothesis that interferon was probably responsible for the observed effect. These results suggest a link between the immune response and DNA repair mechanisms.
我们研究了用干扰素诱导剂聚肌苷酸-聚胞苷酸以及其他细胞因子（白细胞介素-1、肿瘤坏死因子）或细胞因子诱导剂脂多糖处理大鼠肝脏后，对O6-烷基鸟嘌呤-DNA烷基转移酶（AT）的影响。以N-[3H]甲基-N-亚硝基脲烷基化的小牛胸腺DNA为底物，采用高效液相色谱法测定肝提取物中O6-甲基鸟嘌呤的含量，从而确定AT水平。腹腔注射低至0.1mg/kg的聚肌苷酸-聚胞苷酸可使肝脏中AT水平显著升高（P<0.01），在处理后24小时或48小时即可明显观察到。腹腔注射80μg/kg的脂多糖也可诱导AT产生，而白细胞介素-1（60μg/kg）或肿瘤坏死因子（60μg/kg）则无此作用。用人重组干扰素αA/D处理可使AT水平显著升高，从而证实了干扰素可能是导致上述观察结果的原因这一假说。这些结果表明免疫反应与DNA修复机制之间存在联系。
