Anti-recombinogenic and convertible co-mutagenic effects of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and other 5-substituted pyrimidine nucleoside analogs in S. cerevisiae MP1.
In experiments using yeast, without addition of an external metabolic activation system, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was co-mutagenic and showed an insignificant anti-recombinogenic effect in combination with triethylene melamine (TEM). In the presence of activating S9-mix, the anti-recombinogenicity and co-mutagenicity could clearly be seen. At higher concentrations the co-mutagenic effect was converted into anti-mutagenicity. The other three 5-substituted pyrimidine nucleoside analogs were tested only in the presence of activating S9-mix and showed similar effects. As TEM is a direct alkylating agent that is inactivated by liver microsomes, the higher activity in presence of S9-mix can be interpreted as resulting from metabolic activation of the 5-substituted pyrimidine nucleoside analogs. In previous experiments using yeast bacteria, Drosophila or mice, tumor promoters were co-recombinogenic/anti-mutagenic, and co-carcinogens were co-mutagenic/anti-recombinogenic. Thus, there is not only an operational difference between tumor promoters and co-carcinogens but a real difference in respect to their genetic effectiveness. As up to now only co-carcinogens have shown co-mutagenic and anti-recombinogenic effects, it is perhaps possible that, within a certain concentration range, 5-substituted pyrimidine nucleoside analogs may have co-carcinogenic activity in carcinogenicity tests. At higher concentrations the co-carcinogenic effect may be converted into an anti-carcinogenic one.
Fahrig
R
R
Department of Genetics, Fraunhofer-Institute for Toxicology and Aerosol Research, Hannover, Germany.
D000818:Animals; D001972:Bromodeoxycytidine / Q000031:analogs & derivatives; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005800:Genes, Fungal; D006579:Heterozygote; D007065:Idoxuridine / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D051381:Rats; D011995:Recombination, Genetic / Q000187:drug effects*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D014265:Triethylenemelamine / Q000633:toxicity; D014271:Trifluridine / Q000633:toxicity
D009153:Mutagens; D003841:Deoxycytidine; D001972:Bromodeoxycytidine; C020235:brivudine; C011288:ibacitabine; D014265:Triethylenemelamine; D001973:Bromodeoxyuridine; D007065:Idoxuridine; D014271:Trifluridine