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

Zidovudine, the anti-AIDS drug, caused inhibition of mitogen-induced proliferation 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 apo-direct analysis, cells showed apoptosis in G0/G1 phase. In DNA gel analysis, characteristic laddering of apoptosis was observed in AZT-treated bone marrow cells. We demonstrated that, when the animals were pretreated with protein A (PA) of Staphylococcus aureus, the apoptotic changes could be prevented in bone marrow cells of AZT-treated animals. There is a significant (p < 0.05) increase in proliferation of bone marrow cells subjected to mitogen treatment in PA+AZT-treated animals, compared to only AZT-treated animals. However, cell-cycle phase distribution was not hampered and no laddering in DNA gel analysis was also observed in this group. In apo-direct analysis, PA treatment showed significant (p < 0.001) inhibition of AZT-induced apoptosis. These observations indicate that by using a suitable agent such as protein A the toxic side effects of AZT could be minimized. Copyright 1999 Academic Press.