Dose-response study of the carcinogenicity of tobacco-specific N-nitrosamines in F344 rats

D. Hoffmann, A. Rivenson, Shantu Amin, S. S. Hecht

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Tobacco and tobacco smoke contain relatively high amounts of four tobacco-specific N-nitrosamines. Of these, N-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N′-nitrosoanatabine (NAT) were bioassayed at three dose levels by subcutaneous injections into male and female F344 rats in 60 subdoses amounting in total to 9, 3, and 1 mmol/kg. Compared with the solvent control group (trioctanoin), both NNN and NNK induced significant numbers of tumors of the nasal cavity (P<0.01) at all three dose levels in both male and female rats. Significant numbers of tumors were also induced by NNK in the lung at all three dose levels and in the liver at the highest dose level (P<0.05). In addition to nasal tumors NNN also induced esophageal tumors at a significant rate in male rats at the high and medium dose levels and in female rats at the high level (P<0.05); NAT was inactive at the three doses tested. Bioassays at lower dose levels as well as biochemical studies are strongly indicated for NNN and NNK since these nitrosamines occur in relatively high amounts in both chewing tobacco and tobacco smoke.

Original languageEnglish (US)
Pages (from-to)81-86
Number of pages6
JournalJournal of Cancer Research and Clinical Oncology
Volume108
Issue number1
DOIs
StatePublished - Jul 1 1984

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N'-nitrosonornicotine
Nitrosamines
Inbred F344 Rats
Tobacco
Smoke
Neoplasms
Smokeless Tobacco
Nasal Cavity
Subcutaneous Injections
Nose
Biological Assay
Lung
Control Groups
Liver

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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title = "Dose-response study of the carcinogenicity of tobacco-specific N-nitrosamines in F344 rats",
abstract = "Tobacco and tobacco smoke contain relatively high amounts of four tobacco-specific N-nitrosamines. Of these, N-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N′-nitrosoanatabine (NAT) were bioassayed at three dose levels by subcutaneous injections into male and female F344 rats in 60 subdoses amounting in total to 9, 3, and 1 mmol/kg. Compared with the solvent control group (trioctanoin), both NNN and NNK induced significant numbers of tumors of the nasal cavity (P<0.01) at all three dose levels in both male and female rats. Significant numbers of tumors were also induced by NNK in the lung at all three dose levels and in the liver at the highest dose level (P<0.05). In addition to nasal tumors NNN also induced esophageal tumors at a significant rate in male rats at the high and medium dose levels and in female rats at the high level (P<0.05); NAT was inactive at the three doses tested. Bioassays at lower dose levels as well as biochemical studies are strongly indicated for NNN and NNK since these nitrosamines occur in relatively high amounts in both chewing tobacco and tobacco smoke.",
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Dose-response study of the carcinogenicity of tobacco-specific N-nitrosamines in F344 rats. / Hoffmann, D.; Rivenson, A.; Amin, Shantu; Hecht, S. S.

In: Journal of Cancer Research and Clinical Oncology, Vol. 108, No. 1, 01.07.1984, p. 81-86.

Research output: Contribution to journalArticle

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