A comparative study of the anticlastogenic effects of chlorophyllin on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or 7,12-dimethylbenz (α) anthracene (DMBA) induced micronuclei in mammalian cells in vitro and in vivo

Toxicol Lett. 2012 Nov 15;214(3):235-42. doi: 10.1016/j.toxlet.2012.08.023. Epub 2012 Sep 15.

Abstract

Chlorophyllin (CHL), a water soluble derivative of chlorophyll has been shown to have both anticarcinogenic and antigenotoxic properties. We evaluated the protective effects of CHL (25μM in vitro, 4 and 100mg/kg. b.w.) on the clastogenic action of two model carcinogens, MNNG and DMBA (25μM and 2μM respectively) in vitro on human hepatoma cells (HepG2) and (40mg and 25mg/Kg/b.w. respectively) in vivo on bone marrow of mice, using the frequencies of induced micronuclei as the end point. Pre-, post- and simultaneous treatments with CHL and the carcinogen were carried out in vitro. With MNNG, only simultaneous treatment with CHL was effective in reducing the frequencies of MN, suggesting a direct interaction between CHL and MNNG. A statistically significant reduction in of DMBA induced MN was found by pre-or post treatment with CHL while a reduction (not significant) was observed by simultaneous treatment. In in vivo experiments, CHL pre-treatment did not affect the frequencies of MN in PCEs of bone marrow induced by MNNG or DMBA. However, increased the toxic effect of DMBA (reduction in percent of PCEs) was accompanied by a reduction in the induced frequencies of MN. CHL was not clastogenic in both in vitro and in vivo tests. It can be concluded that (a) CHL has a protective effect against MNNG and DMBA. This effect is dependent upon the protocol employed in in vitro experiments. In vivo, CHL did not have a protective effect against MNNG and DMBA. A protective effect of CHL against DMBA was evident only at high toxic levels.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity*
  • Animals
  • Antimutagenic Agents / chemistry
  • Antimutagenic Agents / pharmacology*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chlorophyllides / chemistry
  • Chlorophyllides / pharmacology*
  • Cytokinesis / drug effects
  • DNA Damage / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Antagonism
  • Formazans / metabolism
  • Hep G2 Cells
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Liver Neoplasms
  • Male
  • Methylnitronitrosoguanidine / chemistry
  • Methylnitronitrosoguanidine / toxicity*
  • Mice
  • Micronuclei, Chromosome-Defective / chemically induced*
  • Mutagens / chemistry
  • Mutagens / toxicity*
  • Tetrazolium Salts / metabolism

Substances

  • Antimutagenic Agents
  • Chlorophyllides
  • Formazans
  • Mutagens
  • Tetrazolium Salts
  • Methylnitronitrosoguanidine
  • MTT formazan
  • 9,10-Dimethyl-1,2-benzanthracene
  • chlorophyllin