Genotoxicity of purine acyclic nucleotide analogs.
The genotoxic and embryotoxic effects of phosphonomethoxyalkylpurines, a new group of antiviral agents, decrease in the following order: PMEG > PMEthioG > PMEDAP > PMEA > (R)-PMPDAP = (R)-PMPA. Results of the present study are fully consistent with the previously found efficacy of their diphosphates to inhibit the replicative DNA polymerases. The marked genotoxicity of PMEG and PMEthioG is comparable to that of mitomycin C, whereas the moderate genotoxicity of PMEA is comparable to that of AZT. (R)-PMPDAP and (R)-PMPA did not induce any structural aberrations of chromosomes under the experimental conditions.
Otová
B
B
Department of Biology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
Holý
A
A
Votruba
I
I
Sladká
M
M
Bílá
V
V
Mejsnarová
B
B
Lesková
V
V
D000225:Adenine / Q000031:analogs & derivatives / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000633:toxicity*; D002460:Cell Line; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D008297:Male; D015394:Molecular Structure; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000633:toxicity; D011687:Purines / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D000068698:Tenofovir; D013723:Teratogens / Q000737:chemistry / Q000633:toxicity; D013866:Thioguanine / Q000737:chemistry / Q000633:toxicity
C090125:9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine; D000998:Antiviral Agents; D009153:Mutagens; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D011687:Purines; D013723:Teratogens; C063380:9-((2-phosphonylmethoxy)ethyl)guanine; C059499:9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine; D006147:Guanine; C053001:adefovir; D000068698:Tenofovir; D013866:Thioguanine; D000225:Adenine