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Influence of the carboxylesterase inhibitor bis-p-nitrophenylphosphate on the rates of hydrolysis of various α-esters of 1-(N-methyl-N-nitrosamino)-methanol in vitro and in vivo and on the acute toxicity and carcinogenicity of 1-(N-methyl-N-nitrosamino)-methylacetate

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Summary

The effect of an in vivo treatment with the carboxylesterase inhibitor bis-p-nitrophenylphosphate (BNPP) on the hydrolysis of 1-(N-methyl-N-nitrosamino)-methylacetate (NNMA), 1-(N-methyl-N-nitrosamino)-methylbutyrate (NNMB), 1-(N-methyl-N-nitrosamino)-methylbenzoate (NNMBz) and 1-(N-methyl-N-nitrosamino)-methylpivaloate (NMMP) in rat tissue homogenates was studied. The rates of hydrolysis were specific for each compound and different in every organ tested; the extent of inhibition of the hydrolysis by BNPP was also substrate and organ specific. In some cases no inhibition at all was observed. The rate of elimination of NNMA, NNMB, and NNMP from blood was not influenced by BNPP pretreatment. The LD50 of NNMA after i.v. application showed a rise of 85% with a BNPP pretreatment. BNPP also influenced the carcinogenicity of NNMA, whereby the total carcinogenic potency was not altered, but the organotropism had changed slightly.

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Abbreviations

NNMA:

1-(N-methyl-N-nitrosamino)-methylacetate

NNMB:

1-(N-methyl-N-nitrosamino)-methylbutyrate

NNMBz:

1-(N-methyl-N-nitrosamino)-methylbenzoate

NNMP:

1-(N-methyl-N-nitrosamino)-methylpivaloate

BNPP:

bis-p-nitrophenylphosphate

DSF:

disulfiram

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Author information

Correspondence to N. Frank.

Additional information

Dedicated to Professor Dietrich Schmähl on the occasion of his 60th birthday

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Frank, N., Caesar, R., Scherf, H.R. et al. Influence of the carboxylesterase inhibitor bis-p-nitrophenylphosphate on the rates of hydrolysis of various α-esters of 1-(N-methyl-N-nitrosamino)-methanol in vitro and in vivo and on the acute toxicity and carcinogenicity of 1-(N-methyl-N-nitrosamino)-methylacetate. J Cancer Res Clin Oncol 111, 98–102 (1986). https://doi.org/10.1007/BF00400744

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Key words

  • N-nitrosamino-α-ester
  • Bis-p-nitro-phenylphosphate
  • Metabolism
  • Carcinogenesis
  • Inhibition
  • Organotropism