Genotoxicity studies with pure trans-capsaicin
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- 作者：Chanda ; Sanjay ; Erexson ; Greg ; Riach ; Colin ; Innes ; Dawn ; Stevenson ; Frances ; Murli ; Hemalatha ; et. al.
- 关键词：Capsaicin ; Genotoxicity ; Ames assay ; Micronucleus ; Mouse lymphoma ; Chromosomal aberration
- 刊名：Mutation Research/Genetic Toxicology and Environmental Mutagenesis
- 出版年：2004
- 出版时间：January 10, 2004
- 年：2004
- 卷：557
- 期：1
- 页码：85-97
- 全文大小：125 K
文摘
Both positive and negative effects have been found in classical genetic toxicology assays with capsaicin. However, the capsaicin tested in most studies has been derived from pepper plant extracts, which is likely to display varying degrees of purity and possibly diverse impurity profiles. Therefore, the objective of the series of studies reported here was to test the genotoxic potential of pure, synthetic trans-capsaicin (the only naturally occurring geometric isomer of capsaicin), using four genotoxicity assays widely used to evaluate drug substances. These included the Ames, mouse lymphoma cell mutation, mouse in vivo bone marrow micronucleus and chromosomal aberration in human peripheral blood lymphocytes (HPBL) assays. In the Ames assay, pure trans-capsaicin was not mutagenic to Salmonella typhimurium or Escherichia coli when dissolved in dimethylsulfoxide and tested at concentrations extending into the toxic range. trans-Capsaicin was weakly mutagenic in mouse lymphoma L5178Y cells, in the presence of S9 mix, when dissolved in dimethylsulfoxide and tested at concentrations extending into the toxic range. Limited evidence for very weak activity was also obtained in the absence of S9 mix. trans-Capsaicin did not induce micronuclei in bone marrow cells when tested to the maximum tolerated dose of 800mg/kg per day in male and 200mg/kg per day in female CD-1 mice using a 0h plus 24h oral dosing and 48h sampling regimen. Finally, trans-capsaicin did not induce structural or numerical chromosomal aberrations when evaluated for its ability to induce clastogenicity in blood lymphocytes. Taken together, these data suggest that the genotoxic potential of pure trans-capsaicin is very low, especially as the clinical significance of weak mutagenicity in the mouse lymphoma assay for catechol-moiety containing compounds is unclear. Moreover, the different genotoxicity profiles of pure trans-capsaicin and purified chili pepper extracts suggest that the purity and source of capsaicin should always be an important consideration for toxicological evaluations.