Tax protein of human T-lymphotropic virus type I triggers DNA damage.
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.
Saggioro
D
D
Institute of Oncology, Interuniversity Center for Cancer Research (CIRC), University of Padova, Italy.
Majone
F
F
Forino
M
M
Turchetto
L
L
Leszl
A
A
Chieco-Bianchi
L
L
D000906:Antibodies / Q000494:pharmacology; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000378:metabolism; D004249:DNA Damage; D005455:Fluorescent Antibody Technique; D016356:Gene Products, tax / Q000096:biosynthesis / Q000378:metabolism*; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D016399:Lymphoma, T-Cell; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D016685:Mitomycin / Q000633:toxicity; D010957:Plasmids; D014162:Transfection; D014407:Tumor Cells, Cultured
D000906:Antibodies; D016356:Gene Products, tax; D016685:Mitomycin; D015500:Chloramphenicol O-Acetyltransferase