The Studies Of HIV Tat Protein Influencing Cellular Radio-sensitivity And The Acting Mechanisms

The reduced immune function resulted from human immunodeficiency virus (HIV) infection increases the probability of developing several cancers. The most conspicuous cancers, occurring with over a twenty-fold increase compared with the general population are Kaposi's sarcoma (KS) and non-Hodgkin'slymphoma. Large increases in risk (5 to 20 fold) occur with squamous carcinoma of conjunctiva, Hodgkin's disease and leiomyo -sarcoma in children. Surgical treatment is limited for cancer patients infected by HIV, because of the risk of infection by other pathogens. Thus, radiotherapy is the mainstay of localized treatment for tumors in AIDS patients. There is accumulating evidence that when radiotherapy was given to cancers in AIDS cases, they had more severe tissue reactions and often developed cutaneous toxic effects or increased acute mucosal and skin toxicity to radiation . Laboratory investigations have provided further evidence to support the clinical observations of overt sensitivity to radiotherapy in AIDS patients with Kaposi's sarcoma. For example, fibroblasts derived from skin biopsies of HIV-related Kaposi's sarcoma patients were found to be more radiosensitive than fibroblasts from non-HIV-infected patients. However, the mechanism of increased sensitivity of AIDS cancer patients to radiotherapy is still unclear. Tat is a small unclear protein secreted early after infection and is absolutely required for efficient transcription of HIV-1 provirus and viral replication. Tat is secreted by HIV-infected cells, and taken up by and affects neighbouring cells. This "bystander" effect is able to affect both infected and uninfected cells, therefore is regarded as an important contributory to the pathogenesis of AIDS. In this study, the protential effect of HIV Tat protein cellular radio-sensitivity, and related mechanisms were explored.We employed the cellular model of expressing exogenous HIV-1 tat gene in a human rhabdomyosarcoma cell line, to investigate the effect of Tat protein on cellular...