Evaluation of the genotoxicity of 2,4-dichlorophenoxyacetic acid and its derivatives in mammalian cell cultures

Gollapudi, B. Bhaskar; Charles, Jeffrey M.; Linscombe, V. Ann; Day, Susan; Bus, James S.

doi:10.1016/s1383-5718(99)00075-3

Cited by 42 publications

(10 citation statements)

References 10 publications

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“…1 and 2). This negative response coincides with earlier in vitro and in vivo studies [Fahrig 1974;Vogel and Chandler, 1974;Jenssen and Renberg, 1976;Zetterberg et al, 1977;Simmon, 1979;Charles et al, 1999aCharles et al, ,b, 2000Gollapudi et al, 1999]. The lack of effect of Fe oxidation state on the transformation of 2,4-D agrees with an earlier study on chronic mammalian cell cytotoxicity [Sorensen et al, 2004].…”

Section: Discussionsupporting

confidence: 90%

Modulation of the genotoxicity of pesticides reacted with redox‐modified smectite clay

Sorensen¹,

Stucki²,

Warner³

et al. 2005

Environ and Mol Mutagen

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Pesticides are toxic agents intentionally released into the environment; their use raises public health and environmental concerns. In recent years there has been much attention to the biotic degradation of pesticides. Abiotic mechanisms in the soil can contribute to pesticide degradation yet the toxicological impact of such degradation is unclear. This study combines for the first time an investigation into abiotic mechanisms of degradation coupled with toxicological endpoints in mammalian cells. The genotoxicity of three commonly used agricultural pesticides was assessed before and after exposure to redox-modified clay minerals. The objectives of the study were to determine the genotoxicity of 2,4-dichlorophenoxy acetic acid (2,4-D), dicamba, and oxamyl, using single cell gel electrophoresis with Chinese hamster ovary (CHO) cells, and to determine the effect of the iron oxidation state in clay minerals (ferruginous smectite SWa-1) on the genotoxic potency of the pesticides. 2,4-D alone or following reaction with redox-modified clays did not induce DNA damage in CHO cells. Oxamyl alone induced a concentration-dependent increase in genomic DNA damage; however, its genotoxicity declined after reaction with reduced clay minerals. Dicamba was not genotoxic when directly analyzed. When dicamba was reacted with reduced clay, a concentration-dependent increase in genomic DNA damage was observed. This is the first reported case of a pesticide being converted into a genotoxin after exposure to redox-modified smectites. These data introduce a new paradigm on the interaction between redox-modified clays and pesticide-related environmental genotoxicity.

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Section: Discussionsupporting

confidence: 90%

Modulation of the genotoxicity of pesticides reacted with redox‐modified smectite clay

Sorensen¹,

Stucki²,

Warner³

et al. 2005

Environ and Mol Mutagen

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“…Gollapudi et al [18] investigated the genetic toxicity of 2,4-D 2-butoxyethylester and two salts (2,4-D isopropylamine and 2,4-D triisopropanolamine) in cultured Sprague-Dawley rat cells. The end points used were the induction of chromosomal aberrations in primary cultures of rat lymphocytes and forward mutations at the HGPRT locus of Chinese hamster ovary (CHO) cells with and without S9 activation.…”

Section: Toxicological Studiesmentioning

confidence: 99%

“…The toxicological studies are equivocal. While the traditional in vivo rodent assays are all negative for tumorigenic responses, and a number of in vivo and in vitro studies of potential mutagenicity and clastogenicity are negative [18–20], a number of other in vitro studies have shown weakly positive responses for chromosomal aberrations, sister chromatid exchange [SCE], and increased micronucleus formation and replicative index [21], but typically only at the highest concentrations and/or doses tested exceeding renal transport mechanisms or observed effects were transient. In addition, several studies have demonstrated the ability of 2,4-D to interrupt cellular functions and communication [22, 23], suggesting a potential nongenotoxic mode of action.…”

Section: Introductionmentioning

confidence: 99%

A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment

Stackelberg

2013

Journal of Toxicology

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Chlorophenoxy compounds, particularly 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxy)acetic acid (MCPA), are amongst the most widely used herbicides in the United States for both agricultural and residential applications. Epidemiologic studies suggest that exposure to 2,4-D and MCPA may be associated with increased risk non-Hodgkins lymphoma (NHL), Hodgkin's disease (HD), leukemia, and soft-tissue sarcoma (STS). Toxicological studies in rodents show no evidence of carcinogenicity, and regulatory agencies worldwide consider chlorophenoxies as not likely to be carcinogenic or unclassifiable as to carcinogenicity. This systematic review assembles the available data to evaluate epidemiologic, toxicological, pharmacokinetic, exposure, and biomonitoring studies with respect to key cellular events noted in disease etiology and how those relate to hypothesized modes of action for these constituents to determine the plausibility of an association between exposure to environmentally relevant concentrations of 2,4-D and MCPA and lymphohematopoietic cancers. The combined evidence does not support a genotoxic mode of action. Although plausible hypotheses for other carcinogenic modes of action exist, a comparison of biomonitoring data to oral equivalent doses calculated from bioassay data shows that environmental exposures are not sufficient to support a causal relationship. Genetic polymorphisms exist that are known to increase the risk of developing NHL. The potential interaction between these polymorphisms and exposures to chlorophenoxy compounds, particularly in occupational settings, is largely unknown.

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“…More recently, some authors described a mutagenic and genotoxic potential for 2,4-D which increases the mutation frequency in a concentration-dependent mode (Kumari & Vaidyanath 1989;Pavlica, Pape & Nagy 1991). However, in mammalian cell cultures, other authors did not find evidence ¢ n ¢ s s of genotoxicity for this herbicide (Gollapudi et al . 1999).…”

Section: Introductionmentioning

confidence: 99%

Reactive oxygen species‐mediated enzymatic systems involved in the oxidative action of 2,4‐dichlorophenoxyacetic acid*

Romero‐Puertas

McCarthy

Gómez

et al. 2004

Plant Cell & Environment

117

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Evaluation of the genotoxicity of 2,4-dichlorophenoxyacetic acid and its derivatives in mammalian cell cultures

Cited by 42 publications

References 10 publications

Modulation of the genotoxicity of pesticides reacted with redox‐modified smectite clay

Modulation of the genotoxicity of pesticides reacted with redox‐modified smectite clay

A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment

Reactive oxygen species‐mediated enzymatic systems involved in the oxidative action of 2,4‐dichlorophenoxyacetic acid*

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