Stability and capacity of dimethylnitrosamine-induced 06-methylguanine repair system in rat liver

Ruggero Montesano, Henriette Brésil, Ghyslaine Planche-Martel, Ghyslaine Planche-Martel, Anthony E. Pegg

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Repeated administration of dimethylnitrosamine (DMN) (2 mg/kg for 3 weeks) to BD IV rats results in an increased capacity for the liver to repair O6-methylguanine in DNA, whereas other DNA adducts (7-methylguanine and 3-methyladenine) are not affected. In the experiments reported here, data on the rapidity of action of the enhanced system, its capacity after different challenging doses of [14C]DMN (0.2, 2.0, and 20 mg/kg), and the persistence after cessation of the DMN pretreatment are described. The results show that, after a dose of [14C]DMN (2.0 mg/kg), the increased activity acts very rapidly (10 min) repairing O6-methylguanine as soon as it is formed and that, by 2 hr, 65% of the O6-methyiguanine generated in liver DNA has already been removed. Very little removal of O6-methylguanine occurs within this time in control rats not receiving any DMN pretreatment. The DMN-induced repair activity is of limited capacity, since its effect can be detected after DNA damage induced by 0.2 or 2.0 mg of [14C]DMN per kg, whereas this activity has little impact on the O6-methylguanine generated in liver DNA by 20 mg of [14C]DMN per kg. Upon cessation of the DMN pretreatment, the enhanced repair activity, as determined also by the in vitro activity of the O8-methyltransferase, decays slowly, but after 25 days, the repair activity is still higher than control values. No correlation was observed between increased [3H]thymidine incorporation in liver DNA and increased O6-methylguanine repair, indicating that liver cell proliferation is not necessarily coupled with an elevated methyltransferase level. Research.

Original languageEnglish (US)
Pages (from-to)5808-5814
Number of pages7
JournalCancer Research
Volume43
StatePublished - Dec 1 1983

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Dimethylnitrosamine
Liver
DNA
Methyltransferases
DNA Adducts
Thymidine
DNA Damage
Cell Proliferation
O-(6)-methylguanine

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Montesano, R., Brésil, H., Planche-Martel, G., Planche-Martel, G., & Pegg, A. E. (1983). Stability and capacity of dimethylnitrosamine-induced 06-methylguanine repair system in rat liver. Cancer Research, 43, 5808-5814.
Montesano, Ruggero ; Brésil, Henriette ; Planche-Martel, Ghyslaine ; Planche-Martel, Ghyslaine ; Pegg, Anthony E. / Stability and capacity of dimethylnitrosamine-induced 06-methylguanine repair system in rat liver. In: Cancer Research. 1983 ; Vol. 43. pp. 5808-5814.
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abstract = "Repeated administration of dimethylnitrosamine (DMN) (2 mg/kg for 3 weeks) to BD IV rats results in an increased capacity for the liver to repair O6-methylguanine in DNA, whereas other DNA adducts (7-methylguanine and 3-methyladenine) are not affected. In the experiments reported here, data on the rapidity of action of the enhanced system, its capacity after different challenging doses of [14C]DMN (0.2, 2.0, and 20 mg/kg), and the persistence after cessation of the DMN pretreatment are described. The results show that, after a dose of [14C]DMN (2.0 mg/kg), the increased activity acts very rapidly (10 min) repairing O6-methylguanine as soon as it is formed and that, by 2 hr, 65{\%} of the O6-methyiguanine generated in liver DNA has already been removed. Very little removal of O6-methylguanine occurs within this time in control rats not receiving any DMN pretreatment. The DMN-induced repair activity is of limited capacity, since its effect can be detected after DNA damage induced by 0.2 or 2.0 mg of [14C]DMN per kg, whereas this activity has little impact on the O6-methylguanine generated in liver DNA by 20 mg of [14C]DMN per kg. Upon cessation of the DMN pretreatment, the enhanced repair activity, as determined also by the in vitro activity of the O8-methyltransferase, decays slowly, but after 25 days, the repair activity is still higher than control values. No correlation was observed between increased [3H]thymidine incorporation in liver DNA and increased O6-methylguanine repair, indicating that liver cell proliferation is not necessarily coupled with an elevated methyltransferase level. Research.",
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Montesano, R, Brésil, H, Planche-Martel, G, Planche-Martel, G & Pegg, AE 1983, 'Stability and capacity of dimethylnitrosamine-induced 06-methylguanine repair system in rat liver', Cancer Research, vol. 43, pp. 5808-5814.

Stability and capacity of dimethylnitrosamine-induced 06-methylguanine repair system in rat liver. / Montesano, Ruggero; Brésil, Henriette; Planche-Martel, Ghyslaine; Planche-Martel, Ghyslaine; Pegg, Anthony E.

In: Cancer Research, Vol. 43, 01.12.1983, p. 5808-5814.

Research output: Contribution to journalArticle

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AU - Montesano, Ruggero

AU - Brésil, Henriette

AU - Planche-Martel, Ghyslaine

AU - Planche-Martel, Ghyslaine

AU - Pegg, Anthony E.

PY - 1983/12/1

Y1 - 1983/12/1

N2 - Repeated administration of dimethylnitrosamine (DMN) (2 mg/kg for 3 weeks) to BD IV rats results in an increased capacity for the liver to repair O6-methylguanine in DNA, whereas other DNA adducts (7-methylguanine and 3-methyladenine) are not affected. In the experiments reported here, data on the rapidity of action of the enhanced system, its capacity after different challenging doses of [14C]DMN (0.2, 2.0, and 20 mg/kg), and the persistence after cessation of the DMN pretreatment are described. The results show that, after a dose of [14C]DMN (2.0 mg/kg), the increased activity acts very rapidly (10 min) repairing O6-methylguanine as soon as it is formed and that, by 2 hr, 65% of the O6-methyiguanine generated in liver DNA has already been removed. Very little removal of O6-methylguanine occurs within this time in control rats not receiving any DMN pretreatment. The DMN-induced repair activity is of limited capacity, since its effect can be detected after DNA damage induced by 0.2 or 2.0 mg of [14C]DMN per kg, whereas this activity has little impact on the O6-methylguanine generated in liver DNA by 20 mg of [14C]DMN per kg. Upon cessation of the DMN pretreatment, the enhanced repair activity, as determined also by the in vitro activity of the O8-methyltransferase, decays slowly, but after 25 days, the repair activity is still higher than control values. No correlation was observed between increased [3H]thymidine incorporation in liver DNA and increased O6-methylguanine repair, indicating that liver cell proliferation is not necessarily coupled with an elevated methyltransferase level. Research.

AB - Repeated administration of dimethylnitrosamine (DMN) (2 mg/kg for 3 weeks) to BD IV rats results in an increased capacity for the liver to repair O6-methylguanine in DNA, whereas other DNA adducts (7-methylguanine and 3-methyladenine) are not affected. In the experiments reported here, data on the rapidity of action of the enhanced system, its capacity after different challenging doses of [14C]DMN (0.2, 2.0, and 20 mg/kg), and the persistence after cessation of the DMN pretreatment are described. The results show that, after a dose of [14C]DMN (2.0 mg/kg), the increased activity acts very rapidly (10 min) repairing O6-methylguanine as soon as it is formed and that, by 2 hr, 65% of the O6-methyiguanine generated in liver DNA has already been removed. Very little removal of O6-methylguanine occurs within this time in control rats not receiving any DMN pretreatment. The DMN-induced repair activity is of limited capacity, since its effect can be detected after DNA damage induced by 0.2 or 2.0 mg of [14C]DMN per kg, whereas this activity has little impact on the O6-methylguanine generated in liver DNA by 20 mg of [14C]DMN per kg. Upon cessation of the DMN pretreatment, the enhanced repair activity, as determined also by the in vitro activity of the O8-methyltransferase, decays slowly, but after 25 days, the repair activity is still higher than control values. No correlation was observed between increased [3H]thymidine incorporation in liver DNA and increased O6-methylguanine repair, indicating that liver cell proliferation is not necessarily coupled with an elevated methyltransferase level. Research.

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Montesano R, Brésil H, Planche-Martel G, Planche-Martel G, Pegg AE. Stability and capacity of dimethylnitrosamine-induced 06-methylguanine repair system in rat liver. Cancer Research. 1983 Dec 1;43:5808-5814.