Long-term persistence of DNA alkylation in hamster tissues after N-nitrosobis(2-oxopropyl)amine

J. Bax, P. M. Pour, D. L. Nagel, Terence A Lawson, R. A. Woutersen, E. Scherer

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The persistence of 7- and O6-alkylation of guanine in DNA of cell nuclei of male Syrian hamster pancreas, liver, kidneys, lungs [target tissues of N-nitrosobis (2-oxopropyl)amine (BOP)] and salivary glands (nontarget tissue) was studied immunocytochemically 6 h, 1, 3, 7, 14, 28, and 56 days after a single s.c. injection of 20 mg BOP/kg. Conventional antisera raised against O6-methylguanine and imidazole-ring-opened 7-methylguanine were used. Persistent alkyl-specific staining was observed for up to 7 days (7-alkylguanine) or 56 days (O6-alkylguanine) in inter- and intralobular duct cells and centro-acinar cells of the pancreas, periportal hepatocytes and bile duct cells of the liver, cells of the proximal convoluted tubules of the renal cortex, and bronchiolar Clara and alveolar cells in the lungs. Both adducts disappeared from centrilobular liver cells within 1 day, from pancreatic acinar cells within 3 days, and from ducts and acini of the submandibular salivary glands within 14 days after BOP treatment. A high level of persistent O6-alkylation of guanine was related with a high tumor incidence only in case of the ductal/ductular system of the pancreas, the main target tissue of BOP-induced carcinogenesis. The relatively weak carcinogenicity of BOP in other tissues with long-term persistence of O6-alkylguanine in DNA indicates that the formation and persistence of DNA alkylation are not sufficient to account for the carcinogenic organotropism of BOP. Additional factors, such as cell proliferation, appropriate promoting stimuli and the (onco)genes critically involved, may be as important as the modification of DNA.

Original languageEnglish (US)
Pages (from-to)149-155
Number of pages7
JournalJournal of Cancer Research and Clinical Oncology
Volume116
Issue number2
DOIs
StatePublished - Mar 1 1990

Fingerprint

nitrosobis(2-oxopropyl)amine
Alkylation
Cricetinae
Pancreas
Acinar Cells
DNA
Guanine
Salivary Glands
Liver
Alveolar Epithelial Cells
Lung
Proximal Kidney Tubule
Submandibular Gland
Mesocricetus
Bile Ducts
Cell Nucleus
Immune Sera
Hepatocytes
Carcinogenesis
Cell Proliferation

Keywords

  • Alkylation
  • Alkylguanines
  • Hamster
  • Immunocytochemistry
  • Kidney
  • Liver
  • Lung
  • Nitrosamines
  • Pancreas

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Long-term persistence of DNA alkylation in hamster tissues after N-nitrosobis(2-oxopropyl)amine. / Bax, J.; Pour, P. M.; Nagel, D. L.; Lawson, Terence A; Woutersen, R. A.; Scherer, E.

In: Journal of Cancer Research and Clinical Oncology, Vol. 116, No. 2, 01.03.1990, p. 149-155.

Research output: Contribution to journalArticle

Bax, J. ; Pour, P. M. ; Nagel, D. L. ; Lawson, Terence A ; Woutersen, R. A. ; Scherer, E. / Long-term persistence of DNA alkylation in hamster tissues after N-nitrosobis(2-oxopropyl)amine. In: Journal of Cancer Research and Clinical Oncology. 1990 ; Vol. 116, No. 2. pp. 149-155.
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abstract = "The persistence of 7- and O6-alkylation of guanine in DNA of cell nuclei of male Syrian hamster pancreas, liver, kidneys, lungs [target tissues of N-nitrosobis (2-oxopropyl)amine (BOP)] and salivary glands (nontarget tissue) was studied immunocytochemically 6 h, 1, 3, 7, 14, 28, and 56 days after a single s.c. injection of 20 mg BOP/kg. Conventional antisera raised against O6-methylguanine and imidazole-ring-opened 7-methylguanine were used. Persistent alkyl-specific staining was observed for up to 7 days (7-alkylguanine) or 56 days (O6-alkylguanine) in inter- and intralobular duct cells and centro-acinar cells of the pancreas, periportal hepatocytes and bile duct cells of the liver, cells of the proximal convoluted tubules of the renal cortex, and bronchiolar Clara and alveolar cells in the lungs. Both adducts disappeared from centrilobular liver cells within 1 day, from pancreatic acinar cells within 3 days, and from ducts and acini of the submandibular salivary glands within 14 days after BOP treatment. A high level of persistent O6-alkylation of guanine was related with a high tumor incidence only in case of the ductal/ductular system of the pancreas, the main target tissue of BOP-induced carcinogenesis. The relatively weak carcinogenicity of BOP in other tissues with long-term persistence of O6-alkylguanine in DNA indicates that the formation and persistence of DNA alkylation are not sufficient to account for the carcinogenic organotropism of BOP. Additional factors, such as cell proliferation, appropriate promoting stimuli and the (onco)genes critically involved, may be as important as the modification of DNA.",
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AU - Woutersen, R. A.

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