Cytogenetic effects of propyl gallate in CHO-K1 cells.
We investigated whether propyl gallate (PG) can induce sister-chromatid exchanges (SCEs) and chromosomal aberrations (CAs) in CHO-K1 cells. In the absence of an exogeneous metabolizing system, treatments with 0.25-1.5mM PG in plugged flasks for 3h resulted in increases in SCEs, CAs, and endoreduplications (ERDs), which were followed by an increase in the percentage of cells showing cell-cycle delay. At the end of the treatment, a decrease in PG concentration and production of PG dimer and ellagic acid (EA) in the medium were detected, indicating that PG had autoxidized. EA, an oxide of PG, was not genotoxic even at 0.3mM, the maximum concentration soluble in the medium. Several oxygen radical scavengers (superoxide dismutase (SOD), catalase, glutathione and o-phenanthroline (OP)) and an inhibitor of catalase activity (3-amino-1,2,4-triazole (AT)), did not significantly influence PG genotoxicity. When PG autoxidation was suppressed by low pH (6.8) or a 5% CO(2) atmosphere, cell-cycle delay intensified and induction of SCEs and CAs occurred even at the lowest PG dose (0.1mM). When PG (0.5mM) was assayed in the presence of S9 (1.5-9%), gallic acid (GA), a metabolite of PG, was generated in direct proportion to the S9 concentration, while cell-cycle delay and genotoxic effects varied inversely with S9 concentration at the levels over 3%. GA also autoxidized and at >or=0.5mM it induced SCEs. Both catalase and AT suppressed the induction of SCEs by GA or inhibited cell proliferation, indicating that H(2)O(2) participated in the effects. In conclusion, PG in the presence or absence of S9 can induce SCEs, CAs, and ERDs, and the oxides, metabolites and oxygen-free radicals generated during the treatment are partly responsible for these effects.
Tayama
S
S
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, 3-24-1 Hyakunincho, Shinjuku-ku, Tokyo 169-0073, Japan. nawai@tokyo-eiken.go.jp
Nakagawa
Y
Y
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002374:Catalase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D006224:Cricetinae; D020732:Cytogenetic Analysis; D004305:Dose-Response Relationship, Drug; D004610:Ellagic Acid / Q000032:analysis / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005707:Gallic Acid / Q000378:metabolism / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D008297:Male; D009152:Mutagenicity Tests; D010084:Oxidation-Reduction; D011435:Propyl Gallate / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D004610:Ellagic Acid; D005707:Gallic Acid; D011435:Propyl Gallate; D002374:Catalase; D000640:Amitrole