Saggioro D, Majone F, Forino M, Turchetto L, Leszl A, Chieco-Bianchi L
Institute of Oncology, Interuniversity Center for Cancer Research (CIRC), University of Padova, Italy.
Leuk Lymphoma. 1994 Jan;12(3-4):281-6. doi: 10.3109/10428199409059600.
Previous findings indicated that in vitro HTLV-I-infected cells are highly susceptible to spontaneous and chemically induced DNA-damage. To further study the role of different virus gene products in inducing chromosome abnormalities, MOLT-3 cells were transiently transfected with a tax expressing plasmid (pTax), and assayed for genetic damage by the micronucleus test. We found that pTax-transfected cells not only had a statistically higher baseline micronucleus value than non-transfected control cells, but also were more susceptible to Mitomycin C (MMC)-induced DNA damage. Furthermore, the use of human serum containing anti-kinetochore antibodies disclosed that tax enhances the clastogenic effect of MMC. No increase in total micronucleus frequency was observed when MMC treatment preceded pTax transfection, thus suggesting that the micronucleus increase might not be due to the additive effect of tax and MMC. These findings indicate that the viral tax protein could play an important role in inducing the chromosome damage frequently observed in HTLV-I-infected cells.
先前的研究结果表明，体外感染HTLV-I的细胞对自发和化学诱导的DNA损伤高度敏感。为了进一步研究不同病毒基因产物在诱导染色体异常中的作用，用表达tax的质粒（pTax）瞬时转染MOLT-3细胞，并通过微核试验检测遗传损伤。我们发现，pTax转染的细胞不仅在统计学上比未转染的对照细胞具有更高的基线微核值，而且对丝裂霉素C（MMC）诱导的DNA损伤更敏感。此外，使用含有抗动粒抗体的人血清发现，tax增强了MMC的致断裂效应。当MMC处理先于pTax转染时，未观察到总微核频率增加，因此表明微核增加可能不是由于tax和MMC的累加效应。这些发现表明，病毒tax蛋白可能在诱导HTLV-I感染细胞中经常观察到的染色体损伤中起重要作用。
