Potential of short chain fatty acids to modulate the induction of DNA damage and changes in the intracellular calcium concentration by oxidative stress in isolated rat distal colon cells

Citation
Sl. Abrahamse et al., Potential of short chain fatty acids to modulate the induction of DNA damage and changes in the intracellular calcium concentration by oxidative stress in isolated rat distal colon cells, CARCINOGENE, 20(4), 1999, pp. 629-634
Citations number
39
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CARCINOGENESIS
ISSN journal
01433334 → ACNP
Volume
20
Issue
4
Year of publication
1999
Pages
629 - 634
Database
ISI
SICI code
0143-3334(199904)20:4<629:POSCFA>2.0.ZU;2-7
Abstract
Short chain fatty acids (SCFA) are considered to be beneficial fermentation products in the gut by exerting trophic effects in non-transformed colon c ells and by slowing proliferation and enhancing differentiation in colonic tumour cells. We have studied the further effects of SCFA on cellular event s of early carcinogenesis, genotoxicity and cytotoxicity in rat distal colo n cells. Cytotoxicity was assessed by measuring trypan blue exclusion and b y determining the H2O2-induced changes in intracellular calcium concentrati on ([Ca2+](i)) using a fluorospectrophotometer and the calcium-sensitive fl uorescent dye Fura-2, The microgel electrophoresis technique (COMET assay) was used to assess oxidative DNA damage. Individual SCFA and physiological SCFA mixtures were investigated for their potential to prevent DNA and cell damage induced by H2O2, For this, freshly isolated colon cells were treate d with H2O2 (100-500 mu M) and 6.25 mM SCFA, We have found 100-500 mu M H2O 2 to cause a fast initial increase in [Ca2+](i), whereafter the levels grad ually further increased, Addition of SCFA did not affect [Ca2+](i) nor did it reduce the H2O2-induced increase in [Ca2+](i), Butyrate and acetate were able to reduce the induction of DNA damage by 100, 200 and 500 mu M H2O2, respectively. In contrast, i-butyrate and propionate were ineffective. The degree of reduction of DNA damage for the two protective SCFA was similar, Physiological mixtures containing acetate, propionate and butyrate in ratio s of 41:21:38 or 75:15:10 that are expected to arise in the colon after fer mentation of resistant starches and pectin, respectively, did not show sign ificant antigenotoxic effects. The major difference between butyrate and ac etate, on one hand, and i-butyrate and propionate, on the other hand, is th at the former compounds are utilized best as energy sources by the colon ce lls. Therefore, our results on antigenotoxicity coupled with the findings o n [Ca2+](i) homeostasis indicate that molecular effects on the energy syste m render these non-transformed, freshly isolated colon cells to be less sus ceptible to H2O2.