Summary
After subcutaneous administration of dipropylnitrosamine (DPN) to Syrian hamsters, gas-liquid chromatographic analysis of the 16-h urine revealed the DPN metabolites, 2-hydroxypropyl-, 2-oxopropyl-, and methylpropylnitrosamines. In a related series of experiments, hamsters received equimolar doses of the above compounds and of N-nitrosobis(2-hydroxypropyl)-amine (BHP) and 2,2′-dimethyldipropylnitrosamine (DMDPN). The metabolites as well as BHP and DMDPN had a weaker effect than did DPN on the rate and/or latency of respiratory tumors. In the respiratory tract, the segmentai tumor distribution and histological types varied according to the compounds. The metabolites of DPN induced additional tumors in the digestive tract. These experiments do not support the concept that the β-oxidized metabolites of DPN are the proximate carcinogens of the parent compound.
Zusammenfassung
Nach subcutaner Gabe von Dipropylnitrosamin (DPN) wurden 2-Hydroxypropyl-, 2-Oxopropyl- und Methylpropylnitrosamin als Metaboliten (durch GLC) im Urin (16 h) von Syrischen Hamstern gefunden. In weiteren Untersuchungen erhielten die Hamster äquimolare Dosen dieser Substanzen und N-Nitrosobis(2-hydroxypropyl)amine (BHP) sowie 2,2′-Dimethyldipropylnitrosamin (DMDPN). Bezüglich Rate und/oder Latenzzeit von Tumoren im Respirationstrakt wiesen die Verbindungen eine schwächere Wirkung als DPN auf. Die Segmentverteilung der Tumoren sowie der histologische Typ waren abhängig von der Substanz. Die Metaboliten von DPN induzierten zusätzlich Tumoren im Verdauungstrakt. Die Experimente unterstützen nicht das Konzept, daß die β-oxydierten Metaboliten von DPN die Proximatcarcinogene der Ausgangsubstanz sind.
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Supported by U.S. Public Health Service contract NO1 CP33278 from the Division of Cancer Cause and Prevention of the National Cancer Institute, NIH
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Althoff, J., Grandjean, C., Pour, P. et al. Comparison of the effect of β-oxidized dipropylnitrosamine metabolites administered at equimolar doses to Syrian hamsters. Z. Krebsforsch. 90, 141–148 (1977). https://doi.org/10.1007/BF00285320
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DOI: https://doi.org/10.1007/BF00285320