Evaluation of the genotoxic potential of selected anti-AIDS treatment drugs at clinical doses in vivo in mice.
Six anti-AIDS drugs were assessed for in vivo genotoxicity and cytotoxicity at human clinical doses with the mouse bone marrow micronucleus assay. These included four dideoxynucleosides (azidothymidine, dideoxycytidine, dideoxyadenosine, and dideoxyinosine), an anthracycline antibiotic (doxorubicin), and a chelating agent (D-penicillamine). Cytological analysis of the mouse bone marrow cells revealed: (i) The dideoxynucleosides and D-penicillamine failed to induce significant number of micronuclei, and except for one of the five doses of dideoxyinosine, none of the dideoxynucleosides were cytotoxic at the doses tested. (ii) Doxorubicin induced micronuclei in a dose-dependent manner which was statistically significant at 4-times the clinical dose but was not cytotoxic at any of the doses tested.
Motimaya
A M
AM
Department of Dermatology, CBRC, Harvard Medical School, Charlestown, MA 02129.
Subramanya
K S
KS
Curry
P T
PT
Kitchin
R M
RM
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D015224:Dideoxynucleosides / Q000627:therapeutic use / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity; D005260:Female; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D010396:Penicillamine / Q000633:toxicity
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D009153:Mutagens; D004317:Doxorubicin; D010396:Penicillamine