Colostrinin decreases spontaneous and induced mutation frequencies at the hprt locus in Chinese hamster V79 cells

Attila Bacsi, Leopolde Aguilera-Aguirre, Peter German, Marian L. Kruzel, Istvan Boldogh

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Colostrinin™ (CLN), a uniform mixture of low-molecular weight, proline-rich polypeptides, induces neurite outgrowth of pheochromocytoma cells, extends the lifespan of diploid fibroblast cells, inhibits beta amyloid-induced apoptosis and resulted in improved cognitive function when administered to Alzheimer's patients. Here we investigated CLN's antimutagenic activity in cells stressed oxidatively or exposed to chemical or physical agents. Our data show that CLN did not alter cell cycle kinetics and cloning efficiency, while it inhibited the development of spontaneous mutations at the coding region of the hypoxanthine phosphoribosyl-transferase (hprt) gene in Chinese hamster V79 cells. In a dose-dependent manner, CLN lowered reactive oxygen species (ROS)-induced frequency of cells resistant to 6-thioguanine (6-TG) to nearly background level. Likewise, CLN decreased the frequency of methyl methanesulfonate- or mitomycin C-induced mutations in V79 cells. Notably, CLN (at 100, 250, and 500 ng per ml concentrations) decreased UVA-induced mutation frequency, while only the highest dose of CLN also decreased significantly the number of UVB-induced 6-TG-resistant mutant cells. Similar results were obtained using cell cultures of human origin. Overall, our data show that CLN significantly lowers the mutation frequency that develops spontaneously or is induced by ROS, chemical and physical agents. CLN itself has no mutagenic activity. Therefore, CLN may be used in human therapies systemically and/or locally for the prevention of diseases associated with sequence alterations in genomic and mitochondrial DNA.

Original languageEnglish (US)
Pages (from-to)249-259
Number of pages11
JournalJournal of Experimental Therapeutics and Oncology
Volume5
Issue number4
StatePublished - Oct 9 2006

Keywords

  • Colostrinin™
  • Genotoxic chemical and physical agents
  • Mutation frequency
  • Oxidative stress

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Cancer Research

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