Genotoxic effect of substituted phenoxyacetic acids.
The potential toxic and mutagenic action of 2,4-dichlorophenoxyacetic acid has been studied in different test systems, and the obtained results range from increased chromosomal damage to no effect at all. We reexamined the effect of this herbicide by simultaneous using three tests based on yeast, transformed hematopoietic, and mouse bone marrow cells. The results obtained demonstrated that 2,4-dichlorophenoxyacetic acid has cytotoxic and mutagenic effects. The positive response of yeast and transformed hematopoietic cells was verified in kinetics and dose-response experiments. The analysis of metaphase chromosomes indicated a statistically proved induction of breaks, deletions, and exchanges after the intraperitoneal administration of 2,4-dichlorophenoxyacetic acid in mice. The study of phenoxyacetic acid and its differently chlorinated derivatives showed that cytotoxicity and mutagenicity are induced by chlorine atoms at position 2 and/or 4 in the benzene ring. The mutagenic effect was abolished by introduction of a third chlorine atom at position 5. Thus 2,4,5-trichlorophenoxyacetic acid was found to have very weak, if any mutagenic effect; however, the herbicide preserved its toxic effect.
Venkov
P
P
Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia. Venkov@obzor.bio21.bas.bg
Topashka-Ancheva
M
M
Georgieva
M
M
Alexieva
V
V
Karanov
E
E
D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000633:toxicity; D015084:2,4-Dichlorophenoxyacetic Acid / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D002713:Chlorine / Q000737:chemistry; D002875:Chromosomes / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006540:Herbicides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008940:Mitotic Index; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D010575:Pesticides / Q000737:chemistry / Q000633:toxicity; D010642:Phenoxyacetates / Q000737:chemistry / Q000633:toxicity*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship
D006540:Herbicides; D009153:Mutagens; D010575:Pesticides; D010642:Phenoxyacetates; D015084:2,4-Dichlorophenoxyacetic Acid; D002713:Chlorine; D015085:2,4,5-Trichlorophenoxyacetic Acid