Genotoxicity of ziram established through wing, eye and female germ-line mosaic assays and the sex-linked recessive lethal test in Drosophila melanogaster

Tripathy, N. K.; Majhi, Bharat Bhusan; Dey, Lara-Sophie; Das, C. C.

doi:10.1016/0165-1218(89)90152-3

Cited by 8 publications

(8 citation statements)

References 30 publications

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“…DEDC has also generated interest as an immuno-modulator for use in adjunct therapy for the treatment of acquired immunodeficiency syndrome (7,8). Animal studies and in vitro investigations of the toxicity of dithiocarbamates and their bis(thiocarbamoyl) disulfides have shown neurotoxic (9)(10)(11)(12)(13), teratogenic (14,15) and mutagenic (14,(16)(17)(18)(19) effects, and decreased fertility (20,21) to be associated with exposure to these compounds. Despite the recognized toxicity of these compounds, their underlying mechanisms have not been established, and the interactions of their metabolities with macromolecules have not been completely delineated.…”

Section: Introductionmentioning

confidence: 99%

Carbon Disulfide Mediated Protein Crosslinking by N,N-Diethyldithiocarbamate

Valentine¹,

Amarnath²,

Amarnath³

et al. 1995

Chem. Res. Toxicol.

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N,N-Diethyldithiocarbamate and its disulfide are used as pesticides, in industrial processes, and as therapeutic agents, providing numerous opportunities for human exposure. Animal studies and in vitro investigations have demonstrated adverse effects following exposure to dithiocarbamates. The ability of dithiocarbamates to decompose to parent amine and CS2 suggests that these adverse effects may be mediated through release of CS2. The toxicity of CS2 is well established, and covalent cross-linking of proteins has been presented as a potential molecular mechanism of CS2 induced neuropathy. In the present investigation the ability of N,N-diethyldithiocarbamate to effect covalent cross-linking of proteins under physiological conditions is examined. Using 13C NMR, cross-linking was observed to proceed through dithiocarbamate formation on protein amino groups followed by the production of bis(thiocarbamoyl) disulfide, dithiocarbamate ester, and thiourea cross-linking structures. The presence of bis(lysyl) thiourea cross-linking structures was verified by complete protein hydrolysis in conjunction with GC/MS. Generation of inter- and intramolecular cross-linking was established using denaturing polyacrylamide gel electrophoresis under reducing conditions and revealed that cross-linking proceeded more rapidly for N,N-diethyldithiocarbamate than for equimolar CS2 under similar conditions. Covalent cross-linking of solubilized neurofilament triplet proteins, the putative neurotoxic targets, was examined. Both N,N-diethyldithiocarbamate and CS2 were able to covalently cross-link the low molecular weight component of the neurofilament triplet proteins, but neither produced intermolecular cross-linking of the medium or high molecular weight component. These results establish that N,N-diethyldithiocarbamate promoted protein cross-linking occurs under physiological conditions and proceeds through liberation of CS2.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Introductionmentioning

confidence: 99%

Carbon Disulfide Mediated Protein Crosslinking by N,N-Diethyldithiocarbamate

Valentine¹,

Amarnath²,

Amarnath³

et al. 1995

Chem. Res. Toxicol.

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“…Zineb, a carbamate fungicide, has been reported to be mutagenic in both somatic and germ-line cells in Drosophila (Tripathy et al, 1988). In another report, the same research group has reported that the fungicide ziram is mutagenic in the wing, eye and female germ-line mosaic assays, and in sex linked recessive lethal test in Drosophila melanogaster (Tripathy et al, 1989). In a more recent study, Franekic et al (1994) reported that ziram, zineb and thiaram are mutagenic in a battery of bacterial test systems.…”

Section: Genotoxic Effects Of Pesticides In Living Organismsmentioning

confidence: 92%

Genotoxicity Testing in Pesticide Safety Evaluation

Mohanty¹,

Mohanty²,

Jena³

et al. 2011

Pesticides in the Modern World - Pests Control and Pesticides Exposure and Toxicity Assessment

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“…Na-Acetyllysine (1 g, 5 mmol) was suspended in 2-propanol (20 mL), and enough water was added to get a clear solution. Sodium hydroxide (5 mL of 1N solution) was added followed by methyl isothiocyanate (0.5 g). The solution was stirred at room temperature for 16 h, washed with ethyl acetate, and evaporated.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, both animal and plant wildlife may be exposed through pesticidal use or accidental release into the environment (2). Teratogenic (3), genotoxic (4,5), and neurotoxic (6) effects have been associated with exposure to dithiocarbamates, and the general cytotoxicity of one monoalkyldithiocarbamate, N-methyldithiocarbamate (NMDC),1 is exemplified by its use as a soil fumigant (7). The toxicity of NMDC to higher forms of life is also evident from the large number of sporting fish and other aquatic life killed following the accidental introduction of a commercial product (metam sodium) containing NMDC into the Sacramento River (8).…”

Section: Introductionmentioning

confidence: 99%

Characterization of Protein Adducts Produced by N-Methyldithiocarbamate and N-Methyldithiocarbamate Esters

Valentine¹,

Amarnath²,

Amarnath³

et al. 1995

Chem. Res. Toxicol.

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The toxicity of N-methyldithiocarbamate may be mediated through decomposition to more biologically active compounds. Two principal products, CS2 and methyl isothiocyanate, have the potential to interact covalently with macromolecules in biological systems. In this investigation the ability of N-methyldithiocarbamate to generate methyl isothiocyanate and CS2 under physiological conditions resulting in acylation and covalent cross-linking of proteins was examined using 13C NMR and GC/MS. Two N-methyldithiocarbamate esters, S-methyl N-methyldithiocarbamate and (N-acetyl-S-methylthiocarbamoyl)cysteine, were also investigated to evaluate the acylating ability of sulfhydryl conjugates of N-methyldithiocarbamate. The predominant and most stable adduct produced by the free dithiocarbamate and its S-substituted esters was methylthiourea on epsilon-lysyl and N-terminal alpha-amino groups. Derivatization on N-terminal amino groups progressed more rapidly for the dithiocarbamate than for its mercapturate. Methylurea protein adducts were also produced by the dithiocarbamate and its esters, suggesting production of methyl isocyanate in the decomposition of N-methyldithiocarbamate. Covalent cross-linking of beta-lactoglobulin by N-methyldithiocarbamate resulting from its decomposition to CS2 was observed using denaturing polyacrylamide gel electrophoresis. These results demonstrate the ability of a monoalkyldithiocarbamate to acylate protein amino groups and effect covalent cross-linking. These processes represent molecular mechanisms that may contribute to the toxicity of this class of compounds.

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Genotoxicity of ziram established through wing, eye and female germ-line mosaic assays and the sex-linked recessive lethal test in Drosophila melanogaster

Cited by 8 publications

References 30 publications

Carbon Disulfide Mediated Protein Crosslinking by N,N-Diethyldithiocarbamate

Carbon Disulfide Mediated Protein Crosslinking by N,N-Diethyldithiocarbamate

Genotoxicity Testing in Pesticide Safety Evaluation

Characterization of Protein Adducts Produced by N-Methyldithiocarbamate and N-Methyldithiocarbamate Esters

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