Summary
The present investigations showed that assumed and established metabolites of dipropylnitrosamine and dibutylnitrosamine reach the Syrian hamster fetus after subcutaneous (s.c.) treatment of their mothers (at day 14 of gestation). The compounds [2-hydroxypropylpropylnitrosamine, HPPN; 2-oxopropylpropylnitrosamine, OPPN; methylpropylnitrosamine, MPN; N-nitrosobis(2-hydroxypropyl)amine, BHP; and 4-hydroxybutylbutylnitrosamine, HBBN] were still present in the examined tissue (maternal blood, placenta, fetus, amniotic fluid) 4–6 h after s.c. injection. The overall incidence of transplacentally induced tumors was lower in the F1- than in the P-generation and comparatively longer latencies were also observed in the F1-generation. However, in some groups low incidences were found of tumors which did not occur in the mothers (i.e., nasal cavities: BHP, HBBN; trachea: HBBN; lungs: HPPN, BHP, HBBN; liver: OPPN, MPN, BHP, HBBN). Compared to exposure at early gestation, the transplacental carcinogenic effect increased at day 14 of gestation. Neoplasms originating in other organs were not associated with a transplacental effect of the examined nitrosamines.
Zusammenfassung
Die Untersuchungen haben gezeigt, daß angenommene sowie gefundene Metaboliten des Dipropyl- und Dibutylnitrosamins die Feten Syrischer Hamster via Placenta nach subcutaner (s.c.) Behandlung der Muttertiere (14. Tag der Tragzeit) erreichen. Die Verbindungen (2-hydroxypropylpropylnitrosamin, HPPN; 2-oxopropylpropylnitrosamin, OPPN; methylpropylnitrosamin, MPN; N-nitrosobis(2-hydroxypropyl)amin, BHP; 4-hydroxybutylbutylnitrosamin, HBBN) waren noch 4–6 Std nach subcutaner Injektion in den untersuchten Geweben (mütterliches Blut, Placenta, Fetus, Fruchtwasser) nachweisbar. Die allgemeine Tumorhäufigkeit transplacentar induzierter Tumoren war geringer in der F1- als in der P-Generation, während vergleichsweise die Latenzzeiten verlängert waren. Darüber hinaus fanden sich jedoch Geschwülste in geringer Häufigkeit bei einigen Gruppen, die bei Muttertieren nicht gefunden wurden (Nasenhöhle: BHP, HBBN; Trachea: HBBN; Lunge: HPPN, BHP, HBBN; Leber: OPPN, MPN, BHP, HBBN). Für den Laryngo-Tracheal-Trakt erhöhte sich die transplacentare carcinogene Wirkung nach Behandlung am 14. Tag der Tragzeit in Vergleich zur Exposition an einem früheren Zeitpunkt der Gestation. Tumoren anderer Organe wurden nicht auf eine transplacentare Wirkung der untersuchten Nitrosamine bezogen.
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Supported by U.S. Public Health Service Contract NO1 CP33278 from the Division of Cancer Cause and Prevention, National Cancer Institute
We thank Nancy Hays for technical assistance and Mardelle Susman for editorial aid.
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Althoff, J., Grandjean, C. & Pour, P. Transplacental effect of nitrosamines in Syrian hamsters. Z. Krebsforsch. 90, 119–126 (1977). https://doi.org/10.1007/BF00285318
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DOI: https://doi.org/10.1007/BF00285318