Multistep alterations of human lymphocytes infected with HTLV-I and then exposed to carcinogens

Normal human lymphocytes achieved continuous growth in IL-2-containing medium in vitro following HTLV-I infection. They showed specific structural abnormalities of certain chromosomes. Subsequent to exposure to MNNG and TPA, or to UV, they achieved autonomous growth (transformation). Alterations in the signal transduction system were observed in transformed cells that showed loss of ability to grow in the medium containing TPA. Additional chromosome abnormalities appeared in transformed cells. These abnormalities were found to cluster to chromosomes that had preexisting structural abnormalities. Changes of the met gene on chromosome 7, to which structural abnormalities were observed clustering, were detected by Southern blot analysis. Environmental carcinogens may work as cofactors to promote transformation of human lymphocytes infected with HTLV-I. The initial change of human lymphocytes caused by HTLV-I integration may be advanced toward neoplastic transformation by their exposure to other carcinogens.