Chlorophyllin is both a positive and negative modifier of mutagenicity.
The mechanism responsible for the modification of mutagenicity by chlorophyllin has been investigated using mutagenic compounds with different mechanisms of action, including the monofunctional alkylating agents, N-methyl-N'-nitrosourea (MNU) and ethylmethanesulphonate (EMS); nitrosamines related to tobacco products, i.e. dimethyl-nitrosamine (DMN), N-nitrosonornicotine (NNN) and 4-(N-methyl-N-nitrosoamino)-1-(3-pyridinyl)-2-butanone (NNK); the polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (B[a]P) and two of its metabolites, i.e. (-)-7 beta,8 alpha-dihydroxy-7,8-dihydrobenzo[a]pyrene (7,8-diol) and (+)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-oxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE); and a complex mutagenic mixture, an extract and subfractions of Swedish moist oral snuff (SMOS). Mutagenicity was monitored with the Ames Salmonella/microsome assays (STY) and hprt V79 point mutation assay (V79). The effects of chlorophyllin on the mutagenicity of the nitrosamines in the STY assays were found to be complex. In the presence of either NNN or NNK, low concentrations of chlorophyllin actually potentiated the mutagenicity > 2-fold. However, at higher, but still non-toxic concentrations, chlorophyllin decreased the mutagenicity of both compounds. The same type of dose-response relationship for chlorophyllin was indicated in the V79 assay system with DMN, although the effect was much weaker. The results with STY were further confirmed by replacing chlorophyllin with another porphyrin compound, hemin. In contrast, biliverdin, a porphyrin structure without the central metal ion, was unable to potentiate the mutagenicity of NNK in STY.(ABSTRACT TRUNCATED AT 250 WORDS)
Romert
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L
Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, Sweden.
Curvall
M
M
Jenssen
D
D
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002460:Cell Line; D002735:Chlorophyllides / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008862:Microsomes, Liver / Q000378:metabolism; D016296:Mutagenesis / Q000187:drug effects*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D009602:Nitrosamines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects
D016587:Antimutagenic Agents; D002735:Chlorophyllides; D009153:Mutagens; D009602:Nitrosamines; C007020:chlorophyllin