Genetic instability of human cells with DNA related to human retrovirus

To elucidate the role of HTLV-I in human neoplasia, DNA was extracted from tumor tissues, cultured cells, and/or sera from 20 HTLV-I seropositive and from 10 seronegative cancer patients, subjected to PCR-PAGE, and analyzed by Southern hybridization. HTLV-I related sequences were detected in tumors of the seropositives with different types of cancer. In the seronegatives, gag related sequences were detected in some tumors, whereas LTR related sequences were detected in only uterus carcinoma and tax related sequences in none of tumors examined. These sequences were detected in tumor cells as well as lymphoid cells by in situ hybridization. Some of these sequences were also detected in cultured fibroblasts derived from ATL patients. Cultured normal human lymphocytes grew continuously in conditioned media following HTLV-I infection, and transformed on exposure to carcinogens. Chromosome changes in transformed cells appeared clustering to chromosomes abnormalized on HTLV-I infection. The frequency of abnormal chromosomes in lymphocytes was significantly higher in the seropositives and in their family members than in seronegative normal donors. The frequency increased with advancement of host age in the seropositives but not in the seronegatives. These findings indicate that some individuals carry HTLV-I related sequences that may be derepressed by host aging and resulted in increasing genetic instability of host cells rendering them increasingly susceptible to carcinogens.