In Vitro Mutagenicity Studies of the Antiretrovirals AZT, Didanosine, and 3TC and a Plant Antiviral Extract Secomet-V Derived from the Trifollium Species

The plant extract Secomet‐V has previously been shown by Kotwal et al. to have potent antiviral activity. It was tested for mutagenecity with the Ames gene mutation test in Salmonella and the chromosome damage (clastogenic) micronucleolus (MN) test in human lymphocytes. These tests predict long‐term carcinogenesis activity of the agents tested. Secomet‐V (with charcoal added) demonstrated weak clastogenic activity, but powerful mutagenic activity in the Ames test with the addition of exogenous metabolic activation. The mutagenic activity of the conventional antiretroviral drugs AZT, Didanosine (DID), and 3TC alone and in dual combinations was also assessed for the first time for Salmonella mutagenicity without any mutagenic effects. AZT, DID, and 3TC have also been tested for MN induction; DID and 3TC resulted negatively, whereas AZT was positive in a dose‐related manner. The dual combinations of AZT and DID, 3TC and DID plus 3TC did not result in any additive or synergistic effect. Purification in the absence of charcoal results in a drastic reduction in extract mutagenicity, which is almost reduced completely by further ultrafiltration (cutoff