Mutagenesis, Vol. 15, No. 2, 133-136,
March 2000
© 2000 UK Environmental Mutagen Society/Oxford University Press
1-Aminobenzotriazole inhibits acrylamide-induced dominant lethal effects in spermatids of male mice
GSF–Institute of Mammalian Genetics, Ingolstaedter Landstraße 1, D-85764, Neuherberg, Germany and 1 University of Medicine and Dentistry of New Jersey, Newark, NJ 07424, USA
Acrylamide (AA) is a germ cell mutagen and induces clastogenic effects predominantly in spermatids of mice. The mechanism of AA clastogenicity has been a matter of dispute. Since the reactivity of AA with DNA is low but is high with proteins containing SH groups, it was suggested that protamine alkylation could be the mechansim of clastogenicity by AA in spermatids. This was substantiated by the observation that the time course of protamine alkylation and dominant lethal effects in spermatids of mice induced by AA was strictly parallel. Another suggestion was that AA may be metabolized by cytochrome P-450 to the epoxide glycidamide (GA), which is then the ultimate DNA-reactive clastogen. This suggestion was based on the similarity of the stage specificity pattern for dominant lethality and heritable translocation induction by AA and GA. To test this latter assumption, 1-aminobenzotriazole (ABT), an inhibitor of P-450 metabolism, was used in the present experiments. Male mice were pretreated with ABT (3x50 mg/kg) on three consecutive days followed by AA treatment (125 mg/kg) on day 4. Parallel groups of animals were treated with AA (125 mg/kg), ABT (3x50 mg/kg) or with the solvent double-distilled water. The experiment was repeated once with slightly varied mating parameters. The results of both experiments showed that ABT inhibited or significantly reduced the AA-induced dominant lethal effects. Thus, the present data support the hypothesis that the AA metabolite GA is the ultimate clastogen in mouse spermatids.
2 To whom correspondence should be addressed.Tel: +49 89 3187 2302; Fax: +49 89 3187 2210; Email: adler{at}gsf.de
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. I. Ghanayem, R. Bai, and L. T. Burka Effect of Dose Volume on the Toxicokinetics of Acrylamide and Its Metabolites and 2-Deoxy-D-glucose Drug Metab. Dispos., February 1, 2009; 37(2): 259 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Besaratinia and G. P. Pfeifer A review of mechanisms of acrylamide carcinogenicity Carcinogenesis, March 1, 2007; 28(3): 519 - 528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.I. Ghanayem, K.L. Witt, L. El-Hadri, U. Hoffler, G.E. Kissling, M.D. Shelby, and J.B. Bishop Comparison of Germ Cell Mutagenicity in Male CYP2E1-Null and Wild-Type Mice Treated with Acrylamide: Evidence Supporting a Glycidamide-Mediated Effect Biol Reprod, January 1, 2005; 72(1): 157 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Balani, P. Li, J. Nguyen, K. Cardoza, H. Zeng, D.-X. Mu, J.-T. Wu, L.-S. Gan, and F. W. Lee EFFECTIVE DOSING REGIMEN OF 1-AMINOBENZOTRIAZOLE FOR INHIBITION OF ANTIPYRINE CLEARANCE IN GUINEA PIGS AND MICE USING SERIAL SAMPLING Drug Metab. Dispos., October 1, 2004; 32(10): 1092 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Besaratinia and G. P. Pfeifer Genotoxicity of Acrylamide and Glycidamide J Natl Cancer Inst, July 7, 2004; 96(13): 1023 - 1029. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Dybing and T. Sanner Risk Assessment of Acrylamide in Foods Toxicol. Sci., September 1, 2003; 75(1): 7 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Besaratinia and G. P. Pfeifer Weak Yet Distinct Mutagenicity of Acrylamide in Mammalian Cells J Natl Cancer Inst, June 18, 2003; 95(12): 889 - 896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Fennell, R. W. Snyder, W. L. Krol, and S. C. J. Sumner Comparison of the Hemoglobin Adducts Formed by Administration of N-Methylolacrylamide and Acrylamide to Rats Toxicol. Sci., February 1, 2003; 71(2): 164 - 175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Park, L. M. Kamendulis, M. A. Friedman, and J. E. Klaunig Acrylamide-Induced Cellular Transformation Toxicol. Sci., February 1, 2002; 65(2): 177 - 183. [Abstract] [Full Text] [PDF]
|
|