Lonidamine: a non-mutagenic antitumor agent.
Lonidiamine is a novel indazole-carboxylic acid with antitumour properties; it has been studied for potential mutagenicity in a comprehensive battery of tests. In assays for the induction of gene mutations in prokaryotes (Ames test) and eukaryotes (induction of HPRT mutations in CHO cells), negative results were obtained. There was no evidence of the induction of chromosomal damage in cultured mammalian cells in vitro. No mutagenic activity was observed in tests for chromosomal damage in vivo, in somatic cells (micronucleus test) or in germinal cells (dominant lethal test). These negative results are consistent with observations indicating that lonidamine affects cellular energy processes, rather than the mechanisms of cell division. The lack of mutagenic properties suggests that lonidamine may present significant advantages in treatment of some tumours, offering a reduced risk of resistant clones, secondary cancer and heritable genetic damage.
Forster
R
R
F. Angelini Research Institute, Rome, Italy.
Campana
A
A
D'Onofrio
E
E
Henderson
L
L
Mosesso
P
P
Scorza Barcellona
P
P
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001711:Biotransformation; D002460:Cell Line; D002869:Chromosome Aberrations; D005260:Female; D005799:Genes, Dominant; D005804:Genes, Lethal; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007191:Indazoles / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; D007191:Indazoles; D009153:Mutagens; D011720:Pyrazoles; D007041:Hypoxanthine Phosphoribosyltransferase; C016371:lonidamine