Metabolism of n' -nitrosonornicotine by cultured rat esophagus

Stephen S. Hecht, Betti Reiss, Dorothy Lin, Gary M. Williams

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Abstract

The metabolism of N'-nitrosonornicotine (NNN), an esophageal carcinogen, by organ cultured F-344 rat esophagus was investigated. The major metabolites were separated by h.p.l.c. and were identified by comparison to standards as 4-hydroxy-1-(3-pyridyl)-1-butanone, 4-hydroxy-4-(3-pyridyl)-1-butanol and 4-oxo-4-(3-pyridyl)butyric acid from 2'-hydroxylation of NNN and 4-hydroxy-4-(3-pyridyl)-butyric acid from 5'-hydroxylation of NNN. These results demonstrate that α-hydroxylation, which leads to electrophilic diazohydroxides, is the major pathway of metabolism of NNN in cultured F-344 rat esophagus. The extents of formation of the metabolites increased with time and the ratio of products resulting from 2'-hydroxylation to those resulting from 5'-hydroxylation was 4.3 after 1 h, 3.9 after 6 h, 3.4 after 24 h and 3.1 after 48 h. F-344 rat liver slices from the same animals produced metabolites of NNN with a 2'/5'-hydroxylation ratio of 1.4. The 2'/5'-hydroxylation ratio in cultured Syrian golden hamster esophagus was 0.3. These results, together with those of parallel studies of NNN metabolism in A/J mouse lung and Syrian golden hamster trachea indicate that among these tissues, F-344 rat esophagus has a unique ability to preferentially hydroxylate the 2'-position of NNN. The results suggest that 2'-hydroxylation is the key step in the metabolic activation of NNN in rat esophagus.

Original languageEnglish (US)
Pages (from-to)453-456
Number of pages4
JournalCarcinogenesis
Volume3
Issue number4
DOIs
StatePublished - Dec 1 1982

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N'-nitrosonornicotine
Hydroxylation
Esophagus
Mesocricetus
pyrazine-2-diazohydroxide
1-Butanol
Trachea

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Metabolism of n' -nitrosonornicotine by cultured rat esophagus. / Hecht, Stephen S.; Reiss, Betti; Lin, Dorothy; Williams, Gary M.

In: Carcinogenesis, Vol. 3, No. 4, 01.12.1982, p. 453-456.

Research output: Contribution to journalArticle

Hecht, Stephen S. ; Reiss, Betti ; Lin, Dorothy ; Williams, Gary M. / Metabolism of n' -nitrosonornicotine by cultured rat esophagus. In: Carcinogenesis. 1982 ; Vol. 3, No. 4. pp. 453-456.
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