methylnitronitrosoguanidine and HTLV-I-Infections

Human T-cell cultures infected with human T-lymphotropic virus type I (HTLV-I) and interleukin-2 (IL-2)-dependent for their continuous growth were treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and then maintained in the medium containing phorbol 12-myristate 13-acetate (TPA). Cells achieved independence from IL-2 but became TPA-dependent for continuous growth. Multiple ultraviolet (UV) irradiations of TPA-dependent cells resulted in their autonomous growth. G-band karyotype analysis revealed multiple chromosomal abnormalities that were seen in cells before and after MNNG treatment and UV irradiations, and those that were only seen in autonomously growing cells. Viral expression was found to be transiently enhanced in association with emergence of certain chromosomal changes. Exposure of HTLV-I infected cells to certain mutagens may promote the occurrence of the specific rearrangement of cellular genes responsible for regulation of cellular and viral replication and may lead these cells to neoplastic transformation.

Topics: Cell Division; Cell Transformation, Viral; Cells, Cultured; Chromosomes; Combined Modality Therapy; DNA, Viral; Female; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Karyotyping; Lymphocytes; Male; Methylnitronitrosoguanidine; Tetradecanoylphorbol Acetate; Ultraviolet Rays