Inhibitory effects of 9-(2-phosphonylmethoxyethyl)adenine and 3'-azido-2',3'-dideoxythymidine on tumor development in mice inoculated intracerebrally with Moloney murine sarcoma virus.
9-(2-Phosphonylmethoxyethyl)adenine (PMEA), a potent inhibitor of human immunodeficiency virus (HIV), caused a dose-dependent suppression of tumor formation, and mortality associated therewith, in 6-day-old NMRI mice inoculated intracerebrally with Moloney murine sarcoma virus (MSV). Even at a dose as low as 1 mg/kg/day, PMEA effected a significant delay in tumor formation. When evaluated in parallel with PMEA, 3'-azido-2',3'-dideoxythymidine (AZT) conferred a comparable tumor-inhibitory effect at a 5- to 10-fold higher dose than PMEA. Prolonged treatment of MSV-infected mice with PMEA resulted in long-term survivors without apparent signs of tumor development. In view of the propensity of HIV to spread to the central nervous system (CNS), the marked activity shown by PMEA against experimental retrovirus infection of the brain in mice points to its potential in the treatment of AIDS and other retrovirus infections of the CNS.
Balzarini
J
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Sobis
H
H
Naesens
L
L
Vandeputte
M
M
De Clercq
E
E
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D051379:Mice; D008980:Moloney murine sarcoma virus; D063065:Organophosphonates; D012513:Sarcoma, Experimental / Q000188:drug therapy*; D012888:Skull Neoplasms / Q000188:drug therapy*; D015215:Zidovudine / Q000008:administration & dosage / Q000494:pharmacology*
D063065:Organophosphonates; D015215:Zidovudine; C053001:adefovir; D000225:Adenine