Mutagenicity of synthetic racemic fecapentaene-12

Göggelmann, W.; Maier, Franz Karl; Pfaendler, H. R.

doi:10.1016/0165-7992(86)90144-2

Cited by 24 publications

(5 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It may be noted, for example, that the SRI group dissolved their test compounds in DMSO, and DMSO has been shown to bring about changes in some test substances under the conditions of the Ames assay (60). The mutagenicity of all-transfecapentaene 12 has also been determined in an independent study, and it was shown to have comparable mutagenicity to natural fecapentaene 12 in TA100 (61).…”

Section: Structure-activity Relationships and Mechanism Of Action Of ...mentioning

confidence: 99%

The fecapentaenes, potent mutagens from human feces

Rl²,

Td³

1990

Chem. Res. Toxicol.

View full text Add to dashboard Cite

Section: Structure-activity Relationships and Mechanism Of Action Of ...mentioning

confidence: 99%

The fecapentaenes, potent mutagens from human feces

Rl²,

Td³

1990

Chem. Res. Toxicol.

View full text Add to dashboard Cite

“…3 It is worth noting, finally, that in the last analysis the biological activity of fecapentaene-12 may not be strongly dependent on its stereochemistry. At least in the Ames test, the activity of the natural product is very similar to that of the racemic synthetic mixture [3 + 5] (13), and also to that of the all-E compound 3 (14). Two synthetic model compounds, one in which a methyl group replaces the glyceryl moiety (15) and one in which the vicinal hydroxyl groups are protected as an acetonide, were also shown to be strong mutagens, albeit at a somewhat reduced level.…”

Section: 48mentioning

confidence: 99%

On the Stereochemistry of Fecapentaene-12

Kingston

Piccariello²,

Duh³

et al. 1988

J. Nat. Prod.

View full text Add to dashboard Cite

“…originate from bacterial modification of polyunsaturated ether phospholipids (5)(6)(7)(8)(9)(10)(11)(12). Synthetic fecapentaene-12 (FP-12*) appears to be highly mutagenic to several strains of Salmonella typhimurium (13)(14)(15) and various genotoxic effects have been observed in murine and mammalian cell types, comprising sister chromatid exchanges (16), mutations at the hypoxanthineguanosine phosphoribosyl transferase locus (16), unscheduled DNA synthesis (17) and DNA single-strand breaks (18,19). However, the mechanism of fecapentaene-induced modification of DNA remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Electron spin resonance spectroscopy of oxygen radicals generated by synthetic fecapentaene-12 and reduction of fecapentaene mutagenicity to Salmonella typhimurium by hydroxyl radical scavenging

Kok

Maanen²,

Lankelma

et al. 1992

Carcinogenesis

View full text Add to dashboard Cite

Fecapentaenes form a class of potent fecal mutagens and have been suggested to play an initiating role in colon carcinogenesis. Although several indications have been found that fecapentaenes may induce oxidative DNA damage as well as DNA alkylation, the mechanism of genotoxicity remains unknown. In this study, electron spin resonance spectroscopy with several spin traps has been used in order to determine whether reactive oxygen species can be formed by fecapentaene-12 (FP-12). No specific conditions could be defined that resulted in the direct formation of oxygen radicals from FP-12. However, peroxidation of FP-12 by various peroxidative enzymes has been shown to result in the formation of superoxide adducts of the spin traps alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Addition of superoxide dismutase resulted in a decreased spectrum intensity, whereas the hydroxyl radical scavenger t-butyl alcohol (tBA) appeared of no influence on the signal, both confirming the formation of superoxide. The formation of hydroxyl radical spin adducts has been demonstrated after peroxidation of FP-12 in incubations with the spin-trapping agent 2,2,6,6-tetramethyl-piperidine (TMP). Further, the effects of scavenging hydroxyl radicals with respect to the genotoxic potential of FP-12 in the Salmonella mutagenicity assay has been investigated. It was clearly shown that radical scavenging reduced the number of revertants in Salmonella strains TA100, TA102 and TA104. This mutagenicity-reducing effect was more convincing using both spin traps DMPO and TMP as compared to the effect of hydroxyl radical scavengers tBA and DMSO. Based on these findings, a reaction scheme is proposed that suggests the formation of superoxide after peroxidation of FP-12, which is subsequently converted to hydroxyl radicals by the iron-catalysed Haber-Weiss reaction.

show abstract

Mutagenicity of synthetic racemic fecapentaene-12

Cited by 24 publications

References 15 publications

The fecapentaenes, potent mutagens from human feces

The fecapentaenes, potent mutagens from human feces

On the Stereochemistry of Fecapentaene-12

Electron spin resonance spectroscopy of oxygen radicals generated by synthetic fecapentaene-12 and reduction of fecapentaene mutagenicity to Salmonella typhimurium by hydroxyl radical scavenging

Contact Info

Product

Resources

About