Summary
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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Abbreviations
- HPLC:
-
high performance liquid chromatography
- NAB:
-
N′-nitrosoanabasinc
- NAT:
-
N′-nitrosoanatabine
- NNK:
-
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
- NNN:
-
N′-nitrosonornicotine
References
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Dedicated to Professor Hermann Druckrey on the occasion of his 80th birthday
This is No. XXVII of “A Study of Tobacco Carcinogenesis”. The study is supported by U.S. National Cancer Institute Grant CA-29580
We thank Ms. Maria Nicholais and Mr. Joel Reinhardt from the Research Animal Facility for their excellent technical assistance
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Hoffmann, D., Rivenson, A., Amin, S. et al. Dose-response study of the carcinogenicity of tobacco-specific N-nitrosamines in F344 rats. J Cancer Res Clin Oncol 108, 81–86 (1984). https://doi.org/10.1007/BF00390978
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DOI: https://doi.org/10.1007/BF00390978