Toxicity of 2,4-dichlorophenoxyacetic acid - molecular mechanisms

• Autorzy: Bukowska B
• Języki publikacji: EN

Abstrakty

EN

2,4-dichlorophenoxyacetic acid (2,4-D) is a herbicide commonly used in agriculture. The residues of 2,4-D are present in air, water, soil and edibles. It constitutes a real hazard for human and animal health as numerous accidents of poisoning deaths caused by this herbicide have been reported. However, the molecular mechanism of its action is still unknown. The point of view concerning the toxic action of 2,4-dichloro-phenoxyacetic acid has been evolving from decades and now it is considered that 2,4-D also induces free radical reactions that lead to numerous unbeneficial changes in tissues. The increases of free radical levels cause DNA damage and thus cell death (in apoptotic process). It is also suggested that 2,4-D causes cell apoptosis as the result of change of membrane potential in mitochondria and initiates caspase-dependent reactions. For many years the discussion has been continuing concerning the mutagenicity of 2,4-D and now many documented investigations that have been performed from 2000 unequivocally proved its mutagenic action. The mutagenicity of 2,4-D concerns homologous recombination, A→G mutation, chromosome aberrations, sister chromatid exchange and DNA damage, and also an increase in the frequency of DNA strand breaks. This paper presents literature data (especially the newest that have been published since 2000) that refer to peroxidative capacity of 2,4-D, free radical formation, induction of apoptosis, genotoxic activity and adaptation of the cells and organisms to its action.

Słowa kluczowe

EN

molecular mechanism; toxicity; herbicide; mutation; free radical; cell adaptation; apoptosis; 2,4-dichlorophenoxyacetic acid

• Wydawca: -
• Czasopismo: Polish Journal of Environmental Studies
• Rocznik: 2006
• Tom: 15
• Numer: 3
• Opis fizyczny: p.365-374,fig.,ref.

Twórcy

autor

Bukowska B

• University of Lodz, Banacha 12/16, 90-237 Lodz, Poland

Bibliografia

• 1. COX C., 2,4-D toxicology. J. Pest. Ref., 19, 14, 1999.
• 2. GARABRANT D.H., PHILBERT M.A., Review of 2,4-dichlorophenoxyacetic acid (2,4-D) epidemiology and toxicology. Crit. Rev. Toxicol. 32, 233, 2002.
• 3. Sierra Club of Canada http://eddenet.pmra-arla.gc.ca/4.0/4.01. asp. 2005.
• 4. BRAND R.M., SP ALDING M., MUELLER C., Sunscreens Can Increase Dermal Penetration of 2,4-Dichlorophenoxyacetic Acid. Clin. Toxicol. 40, 827, 2002.
• 5. WAITE D.T., CESSNA A.J., GROVER R., KERR L.A., SNIHURA A.D. Environmental concentrations of agricultural herbicides: 2,-4-D and triallate. J. Environ. Qual. 31, 129, 2002.
• 6. TIMCHALIK C., Comperative inter-species pharmacokinetics of phenoxyacetic acid herbicides and related organic acids. Evidence that the dog is not a relevant species for evaluation of human health risk. Toxicology 200, 1, 2004.
• 7. STÜRTZ N., EVANGELISTA DE DUFFARD A.M., DUFFARD R., Detection of 2,4-dichlorophenoxyacetic acid (2,4-D) residues in neonates breast-fed by 2,4-D exposed dams. Neurotoxicol. 2, 147, 2000.
• 8. MICHAŁOWICZ J., The occurrence of chlorophenols, chlorocatechols and chlorinated methoxyphenols in drinking water of the largest cities in Poland. Polish Journal of Environmental Studies 14, 327, 2005.
• 9. BUKOWSKA B., KOWALSKA S., The presence and toxicity of phenol derivatives – their effect on human erythrocytes. Current Topics in Biophysics, 27, 43, 2003.
• 10. BUKOWSKA B., DUDA W., STEFAN A., MICHAŁOWICZ J., Molekularne efekty działania Dioksyn. Current Topics in Biophysics, 22, 3, 1998.
• 11. BUKOWSKA B., Damage to the erythrocyte caused by 2,3,7,8- tetrachlorodibenzo-p-dioxin (in vitro). Cell. Mol. Biol. Lett. 9, 261, 2004.
• 12. BRADBERRY S.M., WATT B.E., PROUDFOO T A.T., Vale J.A., Mechanism of toxicity, clinical features and management of acute chlorophenoxy herbicide poisoning: a review. Clin. Toxicol. 38, 111, 2000.
• 13. BURNS C.J., BEARD K.K., CARTMILL l J.B., Mortality in chemical workers potentially exposed to 2,4-dichlorophenoxyacetic acid (2,4-D) 1945-1994 an update. Occup. Environm. Med. 58, 24, 2001.
• 14. PHILL IPS P.J., BODE R.W. Pesticides in surface water runoff in south-eastern New York State, US A: seasonal and stormflow effects on concentrations. Pest. Management Science 60, 531, 2004.
• 15. LU C., FENSKE R.A., SIMCOX N.J., KALMAN D., Pesticide exposure of children in an agricultural community: evidence of household proximity to farmland and take home exposure pathways. Environm.l Res. 84, 290, 2000.
• 16. NISHIOK A M.G., LEWIS R.G., BRINKMAN M.C., BURKHOLDER H.M., HINES C. E., MENKEDICK J.R., Distribution of 2,4-D in air on surface inside residences after lawn applications: Comparing exposure estimates from various media for young children. Environ. Health Persp. 11, 1185, 2001.
• 17. WAITE D.T., BAILEY P., SPROULL J.F., QUIRING D.V., CHAU D.F., BAILEY J., CESS NA A.J., Atmospheric concentrations and dry and wet deposits of some herbicides currently used on the Canadian Prairies. Chemosphere 58, 693, 2005.
• 18. VENKO V P., TOP ASHKA-ANCHEVA M., GEORGIEVA M., ALEXIEVA V., KARANOV E., Genotoxic effects of substituted phenoxyacetic acid. Archives Toxicol. 74, 560, 2000.
• 19. BORTOLOZI A., EVANGELISTA DE DUFFARD A.M., DUFFARD R., ANTONELL I M., Effects of 2,4-dichlorophenoxyacetic acid exposure on dopamine D2 –like receptors in rat brain. Neurotoxicol. Teratol., 26, 599, 2004.
• 20. PISTL J., KOVALKOVIČOVA K., HOLOVSKA V., LEGĞATH J., MIKULA I. Determination of the immunotoxic potential of pesticides on functional activity of sheep leukocytes in vitro. Toxicology 188, 73, 2003.
• 21. TUSCHUL H., SCHWAB C., Cytotoxic effects of the herbicide 2,4-dichlorophenoxyacetic acid in HepG2 cells. Food Chem. Toxicol. 41, 385, 2003.
• 22. ROSSO S.B., CÁCERES A.O., EVANGELISTA DE DUFFARD A.M., DE DUFFARD R.O., QUIROGA S., 2,4-dichlorophenoxyacetic acid disrupts the cytoskeleton and disorganizes the Golgi apparatus of cultured neurons. Toxicol. Sci. 56, 133, 2000.
• 23. BARENEKOW D.E., HAMBURG A.W., PUVANESARAJAH V., GUO M., Metabolism of 2,4-dichlorophenoxyacetic acid in laying hens and lactating goats. J. Agric. Food Chem., 49, 156, 2000.
• 24. CHARLES J.M., HANLEY Jr. T.R., WILSON R.D., VAN RAVENZWAAY B., BUS J. S. Developmental toxicity studies in rats and rabbits on 2,4-dichlorophenoxyacetic acid and its forms. Toxicol. Sci. 60, 121, 2001.
• 25. OSAKI K., MAHLER J.F., HASEMANN J.K., MOOMAW C.R., NICOLETTE M.L., NYSKA A., Unique renal tubule changes induced in rats and mice by the peroxisome proliferators 2,4-dichlorophenoxyacetic acid (2,4-D) and WY -14643. Toxicol. Pathol. 29, 440, 2001.
• 26. BORTOLOZI A., DUFFARD R., EVANGELISTA DE DUFFARD A.M., Asymmetrical development of the monoamine systems in 2,4-dichlorophenoxyacetic acid treated rats. NeuroToxicol. 24, 149, 2003.
• 27. BORTOLOZI A., EVANGELISTA DE DUFFARD A.M., DAJAS F., DUFFARD R., SILVEIRTA R., Intracerebral 2,4-dichlorophenoxyacetic acid-induced alterations in behavioral responses and monoamine levels in adult rats. NeuroToxicol. 22, 221, 2001.
• 28. GARCIA G., TAGLIAFERRO P., FERRI A., EVANGELISTA DE DUFFARD A.M., DUFFARD R., BRUS CO A., Study of tyrosine hydroxylase immunoreactive neurons in neonate rats lactationally exposed to 2,4-dichlorophenoxyacetic acid. Neurotoxicology 25, 951, 2004.
• 29. GANDHI R., WANDJI S., SNEDEKER S., Critical evaluation of cancer risk from 2,4-D. Rev. Environ. Contam. Toxicol. 167, 1, 2000.
• 30. MCDUFFIE H.H., PAHWA P., MC LAUDHLIN J.R., SPINELLI J.J., FINCHAM S., DOSMAN J.A., ROBSON D., SKINNIDER L.F., CHOIN.W., Non-Hodgkins lymphoma and specific pesticide exposure in men: cross-Canada study of pesticides and health. Cancer Epidemiol. Biomarkers Prev. 10, 1155, 2001.
• 31. BUCKLEY J.D., MEADOWS A.T., KADIN M.E., LEBEAU M.M., SIEGIEL S., ROBOSON L.L. Pesticide exposures in children with non-Hodgkin lymphoma. Cancer 1, 2315, 2000.
• 32. HARDELL L., ERIKSSO N M., NORDSTRÖM M., Exposure to pesticides as risk factor for non-Hodgkin’s lymphoma and hairy cell leukemia; pooled analysis of to Swedish case-control studies. Leukemia and Lymphoma 43, 1043, 2002.
• 33. SEGEL G.B., Lichtman M.A., Familial (inherited) leukemia, lymphoma, and myeloma: an overview. Blood Cells, Molecules and Diseases 32, 246, 2004.
• 34. COMEAU Y., GREER C.W., SAMSON R., Role of inoculum preparation and density on the bioremediation of 2,4-D-contamination soil by bioaugmentation. Appl. Microbiol. Biotechnol., 38, 681, 1993.
• 35. DAUGHERTY D.D., KAREL S.F., Degradation of 2,4-dichlorophenoxyacetic acid by Pseudomonas capacia DBO1 (pR01D1) in a Dual-Substrate Chemostat. Applied and Environmential Microbiology, 60, 3261, 1994.
• 36. PETRYCKA H., Microflora and microbiological transformations in biological membrane that removes coke phenolic waters Exercise books of Silesian Polytechnic., Gliwice, pp. 8-13, 1980 (in Polish).
• 37. LEVAN T., Studies on degradations of defoliants 2,4-D and 2,4,5-T by selected soil microorganisms. Exercise books of Hugo Kołłataj Agricultural Academy of Science in Cracov. Habilitation Thesis, 27, 1981 (in Polish).
• 38. HINTEREGGER C., LEITNER R., LOIDL M., FERSCHL A., STREICHSBIER F., Degradation of phenol and phenolic compounds by Pseudomonas putida EKII. Appl. Microbiol. Biotechnol., 37, 252, 1992.
• 39. HINTEREGGER C., LOIDL M., STOCKINGER J., STREICHSBIER F., Enhacement of the bacterial degradation of phenoxyalkanoate herbicides by the use of modified polyurethane foam as a support. J. Basic. Microbiol., 35, 393, 1995.
• 40. GRABIŃSKA-SOTA E., WIŚNIOWSKA E., KALKA J., Toxicity of selected synthetic auxines – 2,4-D and MCPA derivatives to broad-leaved and cereal plants. Crop Protection 22, 355, 2003.
• 41. GWOŹDZIŃSKI K., Instrumental Methods in Biophysic and Biomedic Sciences. The Institute of Physics of Łódź Polytechnic, 2000 (in Polish).
• 42. MATES J.M., Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology. Toxicology 153, 83, 2000.
• 43. KULIKOWSKA-KARPIŃSKA E., MONIUSZKO-JAKONIUK J., The Antioxidative Barrier in the Organism. Polish Journal of Environmental Studies 13, 5, 2004.
• 44. NOWAK E., WYRWICZ G., DĄBROWSKI Z., SMOLEŃSKI O., SPODAREK K. Rheological and biochemical examination of red blond Wells after treatment with different pharmacological and toxic substances. Clinical Hemorheology Microcirculation 26, 91, 2002.
• 45. CHUNG F.L., CHEN H.J., NATH R.G., Lipid peroxidation as a potential endogenous source for the formation of exocyclic DNA adducts. Carcinogenesis 17, 2105, 1996.
• 46. POGOSYAN S.J., NIKOLAI V., SHEVCHENKO N.V., MERZlYAK M.N., Stimulation of NADPH – dependent lipid peroxidation by 2,4-dichlorofenoxyacetic acid and diquat in microsomes isolated from pisum sativum. Plant Science Letters 37, 69, 1984.
• 47. DUCHNOWICZ P., KOTER M., Damage to the erythrocyte membrane caused by chlorophenoxyacetic herbicides. Cell. Mol. Biol. Lett. 8, 25, 2003.
• 48. DUCHNOWICZ P., KOTER M., DUDA W., Damage of erythrocyte by phenoxyacetic herbicides and their metabolites. Pest. Biochem. Physiol. 74, 1, 2002.
• 49. SUWALSKY M., BENITES M., VILL ENA F., AGUILAR F., SOTOMAYO R C.P. Interaction of 2,4-dichlorophenoxyacetic acid (2,4-D) with cell and model membranes. Bioch. Biophys. Acta 1285, 267, 1996.
• 50. DI PAOLO O., DE DUFFARD A.M., DE DUFFARD R., In vivo and in vitro binding of 2,4-dichlorophenoxyacetic acid to a rat liver mitochondrial protein. Chemico-Biol. Int. 137, 229, 2001.
• 51. DUCHNOWICZ P., SZCZEPANIAK P., KOTER M., Erythrocyte membrane protein damage by phenoxyacetic herbicides. Pest. Biochem. Physiol., 82, 59, 2005.
• 52. PUMFORD N.R., HALMES N.C., Protein targets of xenobiotics reactive intermediates. Annu. Rev. Pharmacol. Toxicol. 37, 91, 1997.
• 53. EVANGELISTA DE DUFFARD A.M., FABRA DE PERETTI A, CASTRO DE CANTARINI S, DUFFARD R., Effects of 2,4-dichlorophenoxyacetic acid butyl ester on chick liver. Arch. Environmental Contam. Toxicol. 25, 204, 1993.
• 54. SULIK M., PIŁAT-MARCINKIEWICZ B, SULIK A., BARWIJUK-MACHAŁA M, SULKOWSKA M, BALTAZIAK M, KLEPACKA J., Fetotoxic effect of 2,4-dichlorophenoxyacetic acid (2,4-D) in rats. Rocz. Akad. Med. Bialymst. 43, 298, 1998.
• 55. LI C., GRILLO M.P., BENET L.Z. In vitro studies on the chemical reactivity of 2,4-dichlorophenoxyacetyl-S-acyl-CoA thioester. Toxicol. Appl. Pharmacol., 187, 101, 2003.
• 56. RIVAROLA V.A., BERGESS E J.R., BALEGNO H.F., DNA and protein synthesis inhibition in Chinese Hamster Ovary cells by 2,4-dichlorophenoxyacetic acid. Toxicol. Lett. 29, 137, 1985.
• 57. FABRA A., GIORDANO W., RIVAROL A V., MORI G., CASTRO S., BALEGNO H. The interaction of 2,4-dichlorophenoxyacetic acid, ribosomes and polyamines in Azospirillum brasilense. Toxicology 83, 19, 1993.
• 58. PALMEIRA C.M., MORENO A.J., MADEIRA V.M.C., Thiols metabolism is altered by the herbicides paraquat, dinoseb and 2,4-D: A study in isolated hepatocytes. Toxicol. Lett. 81, 115, 1995.
• 59. BUKOWSKA B., ZATORSKA A., Prehemolytical changes in erythrocytes incubated with 2,4-D. Current Topics in Biophysics, 27, 11, 2003.
• 60. TEIXTEIRA M.C., TELO J.P., DUARTE N.F., SĂ-CORREIA I., The herbicide 2,4-dichlorophenoxyacetic acid induces the generation of free-radicals and associated oxidative stress responses in yeast. Biochem. Biophysical. Res. 324, 1101, 2004.
• 61. ORUC E.O., UNER N., Combined effects of 2,4-D and azinphosmethyl on antioxidant enzymes and lipid peroxidation in liver of Oreochromis niloticus, Comp. Bioch. Physiol. C Toxicol. Pharmacol. 127, 291, 2000.
• 62. ÖZDERM S., ÖZDERM S.S., ALICIGŰZEL Y., The effect of 4-chlorophenoxyacetic acid – raised tomato homogenate on rat erythrocyte antioxidant enzymes. Pest. Biochem. Physiol. 67, 134, 2000.
• 63. ORUC E.O., SEVGILER Y., UNER N., Tissue-specific oxidative stress responses in fish exposed to 2,4-D and azinphosmethyl. Comp. Biochem. Physiol. Part C 137, 43, 2004.
• 64. BUKOWSKA B., CHAJDYS A., DUDA W., DUCHNOWICZ P. Effect of phenoxyherbicides and their metabolites on the activity of catalase in the human erythrocytes. Cell Biol. Int. 24, 705, 2000.
• 65. BUKOWSKA B., Effects of 2,4-D and its metabolite 2,4-dichlorophenol on antioxidant enzymes and level of glutathione in human erythrocytes. Comp. Biochem. Physiol. Part C 135/4, 435, 2003.
• 66. AHMAD I., HAMID T, FATIMA M., CHAND H.S., JAIN S.K., ATHAR M., RAISU DDINET S., Induction of hepatic antioxidants in freshwater catfish (Channa punctatus) is a biomarker of paper mill effluent exposure. Bioch. Biophys. Acta, 1519, 37, 2000.
• 67. BUKOWSKA B., RESZKA E., DUDA W., Influence of phenoxyherbicides and their metabolities on the from of oxy- and deoxyhemoglobin of vertebrates. Biochem. Mol. Biol. Int. 45, 47, 1998.
• 68. MISRA H.P., FRIDOVICH K., The generation of superoxide radical during the autooxidation of hemoglobin. Journal of Biological Chemistry 247, 6960, 1972.
• 69. MADRIGAL-BUJAIDAR E., HERNANDEZ-CERUELOS A., CHAMORRO G., Induction of sister chromatid exchanges by 2,4-dichlorophenoxyacetic acid in somatic and germ cells of mice exposed in vivo. Food Chem. Toxicol. 39, 941, 2001.
• 70. WATAHIKI M.K., MORI H., YAMAMOTO K.T., Inhibitory effects of auxins and related substances on the activity of an Arabidopsis glutathione S-transferase isozyme expressed in Escherichia coli. Physiol. Plant., 94, 566, 1995.
• 71. ARIAS E., Sister chromatid exchange induction by the herbicide 2,4-dichlorophenoxyacetic acid in chick embryos. Ecotoxicol. Environm. Safety, 55, 338, 2003.
• 72. FILKOWSKI J., BESPLUG J., BURKE P., KOVALCHUK I., KOVALCHUK O., Genotoxicity of 2,4-D and dicamba revealed by transgenic Arabidopsis thaliana plants harboring recombination and point mutation markers. Mut. Res. 542, 23, 2003.
• 73. Summary of Guidelines for Canadian Drinking Quality, Health Canada, April 2002.
• 74. TURKALA E., JALAL M., Increased rates of sister chromatid exchanges induced by the herbicide 2,4-D. Journal of Heredity 76, 213, 1985.
• 75. MUSTONEN R., KANGS J., VUOJOLAHTI P., LINNAINMA K., Effects of phenoxyacetic acids on the induction of chromosome aberrations in vitro and in vivo. Mutagenesis 1, 241, 1986.
• 76. PAVLICA M., PAPES D., NAGY B., 2,4-Dichlorophenoxyacetic acid causes chromatin and chromosome abnormalities in plant cells, mutation in cultured mammalian cells. Mut. Res. 263, 77, 1991.
• 77. PILINSCAYA M., Cytogenetic effects of the herbicide 2,4-D on human and animal chromosomes. Tsitologiia Genetica 8, 202, 1974.
• 78. JENSSEN D., RENBERG L., Distribution and cytogenetic test of 2,4-D and 2,4,5-T phenoxy acetic acids in mouse blood tissue. Chemico-Biol. Interac. 14, 291, 1976.
• 79. CHARLES J.M., CUNNY H.C., WILSON R.D., BUS J.S., LAWLOR T.E., CIFONE M. A., FELLOWS M., GOLLAPUDI B., Ames assays and unscheduled DNA synthesis assay on 2,4-dichlorophenoxyacetic acid and its derivatives. Mut. Res. 444, 207, 1999.
• 80. CHARLES J.M., CUNNY H.C., WILSON R.D., IVETT J.L., MURLI H., BUS J.S., GOLLAPUDI B., In vivo micronucleus assays on 2,4-dichlorophenoxyacetic acid and its derivatives. Mut. Res. 444, 227, 1999.
• 81. GOLLAPUDI B.B., CHARLES J.M., LINECOMBE, V.A., DAY S.J., BUS J.S., Evaluation of the genotoxicity of 2,4-dichlorophenoxyacetic acid and its derivatives in mammalian cell cultures. Mut. Res. 444, 217, 1999.
• 82. HOLLAND N.T., DURAMAD P., ROTHMAN N., FIGGS L.W., BLAIR A., HUBBARDA., SMITH M.T., Micronucleus frequency and proliferation in human lymphocytes after exposure to herbicide 2,4-dichlorophenoxyacetic acid in vitro and in vivo. Mut. Res., 521, 165, 2002.
• 83. ZELJEZIC D., GARAJ-VRHOVAC V., Chromosomal aberrations, micronuclei and nuclear buds induced in human lymphocytes by 2,4-dichlorophenoxyacetic acid pesticide formulation. Toxicology 200, 39, 2004.
• 84. ATEEQ B., ABDUL FARAH M., NIAMAT ALI M., AHMAD W., Clastrogenicity of pentachlorophenol, 2,4-D and butachlor evaluated by Allium root tip test. Mut. Res., 514, 105, 2002.
• 85. KAYA B., YANIKOGLU A., MARCOS R., Genotoxicity studies of the phenoxyacetates 2,4-D and 4-CPA in the Drosophila wing spot test. Terat. Carcinogen. Mut., 19, 305, 1999.
• 86. AMER S.M., ALY F.A., Genotoxic effect of 2,4-dichlorophenoxyacetic acid and its metabolite 2,4-dichlorophenol in mouse. Mut. Res., 25, 1, 2001
• 87. ABUL FARAH M., ATEEQ B., NIAMAT ALI M., AHMAD W., Evaluation of genotoxicity of PCP and 2,4-D by micronucleus test on freshwater fish Channa punctatus. Ecotoxicol. Environm. Safety, 54, 25, 2003.
• 88. MIČIĆ M., BIHARI N., MLINARIČ-RAŠČAN I., Influence of herbicide, 2,4-dichlorophenoxy acetic acid, on haemocyte DNA of in vivo treated mussel. Journal of Experimental Marine Biology and Ecology 311, 157, 2004.
• 89. GONZALEZ M., SOLONESK I S., REIGOS A M.A., LARRAMENDY M.L. Genotoxicity of the herbicide 2,4-dichlorophenoxyacetic and a commercial formulation, 2,4-dichlorophenoxyacetic acid dimetylamine salt. I. Evaluation of DNA damage and cytogenetic endpoints in Chinese Hamster Ovary (CHO) cells. Toxicol. in Vitro 19, 289, 2005.
• 90. DE MOLINER K.L., EVANGELISTA DE DUFFARD A.M., SOTO E., DUFFARD R., ADAMO A.M., Induction of apoptosis in cerebellar granule cells by 2,4-dichlorophenoxyacetic acid. Neurochem Res. 27, 1439, 2002.
• 91. KAIOUMOVA D., KAIOUMOV F., OPELZ G., SUS AL C., Toxic effects of the herbicide 2,4-dichlorophenoxyacetic acid on lymphoid organs of the rat. Chemosphere 43, 801, 2001.
• 92. KAIOUMOVA D., SUSAL C., OPELZ G., Induction of apoptosis in human lymphocytes by the herbicide 2,4-dichlorophenoxyacetic acid. Human Immunol. 62, 64, 2001.
• 93. LIN N., GARRY V.F., In vitro studies of cellular and molecular developmental toxicity of adjuvants, herbicides, and fungicides commonly used in Red River Valley, Minnesota. Journal Toxicol. Environm. Health, 60, 423, 2000.
• 94. GOMEZ-LECHON M.J., O’CONNOR E., CASTELL J.V., JOVER R., Sensitive markers used to indentiffy compounds that trigger apoptosis in cultured hepatocytes. Toxicol. Sciences 65, 299, 2002.
• 95. DEL BINO G., DARZYKIEWICZ Z., DEGRAEF C., MOSSELMANS R., FOKAN D., GALAND P. Comparision of methods based on annexin-V binding. DNA content or TUNEL for evaluating cell death in adherent MCF-7 cells. Cell Proliferation 32, 25, 1999.
• 96. OAKES D.J., POLLACK J.K., Affects of a herbicide formulation Tordon 75D, and its individual components on the oxidative functions of mitochondria. Toxicology 136, 41, 1999.
• 97. SULIK M., KISIELEWSKI W., SZYNAKA B., KEMONA A., SULKOWSKA M., BALTAZIAK M. Morphological changes in mitochondria and lysosomes of hepatocytes in acute intoxication with 2,4-dichlorophenoxyacetic acid (2,4- D). Materia Medica Polona 30, 16, 1998.
• 98. OAKES D.J., POLLACK J.K., The in vitro evaluation of the toxicities of three related herbicide formulations containing ester derivatives of 2,4.5-T and 2,4-D using sub-mitochondrial particles. Toxicology 151, 1, 2000.
• 99. RÓŻAŃSKI L. Pesticides transformations in living organisms and the Environment. AGRA-ENVIRO LAB. Poznań pp. 294, 1998 (in Polish).
• 100. SUGAYA S., SAKAI S., Identification of a soluble auxinbinding protein as a gluthatione-dependent formaldehyde dehydrogenase. Plant Science 114, 1 1996.
• 101. CSERHATI T., FORGACS E., DEYL Z., MIKŠIK I. Effect of molecular parametres on the binding of phenoxyacetic acid derivatives to albumins. Journal of Chromatography B 753, 87, 2001.
• 102. MEHMOOD Z., WILLIAMSON M.P., KELLY D.E., KELLY S.L., Human cytochrome P450 3A4 is involved in the biotransformation of the herbicide 2,4-dichlorophenoxyacetic acid. Environm. Toxicol. Pharmacol. 2, 397, 1996.
• 103. FERNANDES A.R., DURAO P.J., SANTOS P.M., SACORREIA I., Activation and significant of vacuolar H+- ATPase in Saccharomyces cerevisiae adaptation and resistance to the herbicide 2,4-dichlorophenoxyacetic acid. Biochem. Biophys. Res. Com. 312, 1317, 2003.
• 104. CASCORBI I., FORET M., Interaction of xenobiotics on the glucose-transport system and the Na+/K+ATPase of human skin fibroblasts. Ecotoxicol. Environ. Saf. 1, 38, 1991.