Protection by protein a of apoptotic cell death caused by anti-AIDS drug zidovudine

Zidovudine, the anti-AIDS drug, caused inhibition of mitogen-induced prolif eration and perturbation of cell-cycle progression of cultured bone marrow cells of mice. There was significant hypoploidy observed in flow cytometric analysis of AZT-treated bone marrow cells. In ape-direct analysis, cells s howed apoptosis in G0/G1 phase. In DNA gel analysis, characteristic ladderi ng of apoptosis was observed in AZT-treated bone marrow cells. We demonstra ted that, when the animals were pretreated with protein A (PA) of Staphyloc occus aureus, the apoptotic changes could be prevented in bone marrow cells of AZT-treated animals. There is a significant (p < 0.05) increase in prol iferation of bone marrow cells subjected to mitogen treatment in PA+AZT-tre ated animals, compared to only AZT-treated animals. However, cell-cycle pha se distribution was not hampered and no laddering in DNA gel analysis was a lso observed in this group. In ape-direct analysis, PA treatment showed sig nificant (p < 0.001) inhibition of AZT-induced apoptosis. These observation s indicate that by using a suitable agent such as protein A the toxic side effects of AZT could be minimized. (C) 1999 Academic Press.