Cell-specific differences of O 6-alkylguanine DNA repair activity during continuous exposure to carcinogen

J. A. Swenberg, M. A. Bedell, K. C. Billings, D. R. Umbenhauer, Anthony Pegg

Research output: Contribution to journalArticle

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Abstract

The activity of the alkyl acceptor protein (AAP) responsible for repair of DNA containing the promutagenic lesion O 6-alkylguanine was determined in hepatocytes and nonparenchymal cells (NPC) obtained from livers of control rats and rats exposed to hepatocarcinogens that primarily induce vascular or hepatocellular neoplasms. Basal levels of AAP activity were found to be 4-5 times higher in hepatocytes than in NPC. Exposure to 1,2-dimethylhydrazine or diethylnitrosamine produced a 2- to 3-fold enhancement of this activity in hepatocytes after exposure for as little as 3 days. The enhanced hepatocyte activity persisted throughout a 28-day exposure to 1,2-dimethylhydrazine. In contrast, AAP activity in NPC was decreased during the first week of exposure to 1,2-dimethylhydrazine and subsequently returned to control levels. No enhancement of AAP was apparent in the NPC. These and related data suggest that enhancement of this activity in rat hepatocytes is a response to cell proliferation. In contrast, the data clearly demonstrate that neither increased cell replication nor the presence of O 6-alkylguanine was capable of enhancing AAP activity in NPC. Cellular differences in the repair of O 6-alkylguanine appear to be a critical mechanism responsible for cell specificity in chemical carcinogenesis by alkylating agents.

Original languageEnglish (US)
Pages (from-to)5499-5502
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume79
Issue number18 I
DOIs
StatePublished - Dec 1 1982

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DNA Repair
Carcinogens
Hepatocytes
1,2-Dimethylhydrazine
Proteins
Diethylnitrosamine
Alkylating Agents
Blood Vessels
Carcinogenesis
Cell Proliferation
Liver
Neoplasms

All Science Journal Classification (ASJC) codes

  • General

Cite this

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title = "Cell-specific differences of O 6-alkylguanine DNA repair activity during continuous exposure to carcinogen",
abstract = "The activity of the alkyl acceptor protein (AAP) responsible for repair of DNA containing the promutagenic lesion O 6-alkylguanine was determined in hepatocytes and nonparenchymal cells (NPC) obtained from livers of control rats and rats exposed to hepatocarcinogens that primarily induce vascular or hepatocellular neoplasms. Basal levels of AAP activity were found to be 4-5 times higher in hepatocytes than in NPC. Exposure to 1,2-dimethylhydrazine or diethylnitrosamine produced a 2- to 3-fold enhancement of this activity in hepatocytes after exposure for as little as 3 days. The enhanced hepatocyte activity persisted throughout a 28-day exposure to 1,2-dimethylhydrazine. In contrast, AAP activity in NPC was decreased during the first week of exposure to 1,2-dimethylhydrazine and subsequently returned to control levels. No enhancement of AAP was apparent in the NPC. These and related data suggest that enhancement of this activity in rat hepatocytes is a response to cell proliferation. In contrast, the data clearly demonstrate that neither increased cell replication nor the presence of O 6-alkylguanine was capable of enhancing AAP activity in NPC. Cellular differences in the repair of O 6-alkylguanine appear to be a critical mechanism responsible for cell specificity in chemical carcinogenesis by alkylating agents.",
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Cell-specific differences of O 6-alkylguanine DNA repair activity during continuous exposure to carcinogen. / Swenberg, J. A.; Bedell, M. A.; Billings, K. C.; Umbenhauer, D. R.; Pegg, Anthony.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 79, No. 18 I, 01.12.1982, p. 5499-5502.

Research output: Contribution to journalArticle

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T1 - Cell-specific differences of O 6-alkylguanine DNA repair activity during continuous exposure to carcinogen

AU - Swenberg, J. A.

AU - Bedell, M. A.

AU - Billings, K. C.

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AU - Pegg, Anthony

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AB - The activity of the alkyl acceptor protein (AAP) responsible for repair of DNA containing the promutagenic lesion O 6-alkylguanine was determined in hepatocytes and nonparenchymal cells (NPC) obtained from livers of control rats and rats exposed to hepatocarcinogens that primarily induce vascular or hepatocellular neoplasms. Basal levels of AAP activity were found to be 4-5 times higher in hepatocytes than in NPC. Exposure to 1,2-dimethylhydrazine or diethylnitrosamine produced a 2- to 3-fold enhancement of this activity in hepatocytes after exposure for as little as 3 days. The enhanced hepatocyte activity persisted throughout a 28-day exposure to 1,2-dimethylhydrazine. In contrast, AAP activity in NPC was decreased during the first week of exposure to 1,2-dimethylhydrazine and subsequently returned to control levels. No enhancement of AAP was apparent in the NPC. These and related data suggest that enhancement of this activity in rat hepatocytes is a response to cell proliferation. In contrast, the data clearly demonstrate that neither increased cell replication nor the presence of O 6-alkylguanine was capable of enhancing AAP activity in NPC. Cellular differences in the repair of O 6-alkylguanine appear to be a critical mechanism responsible for cell specificity in chemical carcinogenesis by alkylating agents.

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