ABSTRACT
The chromosomal aberration test using a Chinese hamster lung cell line (CHL) was carried out on 19 aporphine alkaloids including apomorphine with and without rat liver homogenates (S9) mix. Eighteen of 19 alkaloids tested induced chromosomal aberration in the presence or absence of S9 mix. Among the alkaloids tested, anolobine, liriodenine and 4,5-dioxodehydrocrebanine induced chromosomal aberrations at relatively low concentrations and as low as 2.5, 5 and 3.13 micrograms/ml, respectively. Dicentrine, anolobine and 4,5-dioxodehydrocrebanine induced chromosomal aberrations with high frequencies. Apomorphine induced 10% aberrant cells at 12.5 micrograms/ml in the direct method and 12% at 100 micrograms/ml with S9 mix in the S9 method. Liriodenine which was the most potent mutagen for TA100 with S9 mix and roemerine which was the most potent for TA98 with S9 mix in Ames test were also clastogenic with and without S9 mix.
Subject(s)
Alkaloids/pharmacology , Aporphines/pharmacology , Chromosome Aberrations , Mutagens/pharmacology , Alkaloids/pharmacokinetics , Animals , Aporphines/pharmacokinetics , Biotransformation , Cell Line , Cricetinae , Cricetulus , Mutagenicity Tests , Mutagens/pharmacokineticsABSTRACT
The mutagenicity of 44 isoquinoline alkaloids was tested in Salmonella typhimurium TA100 and TA98 in the presence or absence of S9 mix. The alkaloids tested included compounds from the isoquinoline, benzylisoquinoline, bisbenzylisoquinoline, monoterpene isoquinoline, berberine, morphinane, hasubanan, benzo[c]phenanthridine and aporphine groups. Among the alkaloids tested, liriodenine was the most potent mutagen for TA100 and roemerine was the most potent for TA98. A clear structure-mutagenicity relationship was observed in a series of aporphine alkaloids (aporphine, dehydroaporphine, 7-oxoaporphine and 4,5-dioxoaporphine), and 10,11-non-substituted aporphines were suggested to exert their mutagenicity through metabolic activation of the 10,11 positions, possibly as the 10,11-epoxides.
