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The Expression of Bacterial DNA Alkylation Repair Enzymes in Mer- Human Cells

  • Leona Samson
  • Patrick Carroll
  • Bruce Derfler
  • William Rebeck

Abstract

Simple monofunctional alkylating agents such as methylmethane sulphonate (MMS) and N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) cause a variety of alkylated lesions in DNA, and these lesions can cause the induction of mutation and cell death in both human and bacterial cells. The repair of these DNA alkylation damages reduces cell killing and the induction of mutations and chromosome damage. In E. coli, the repair of 06-methylguanine (06MeG) and 04-methylth5anine (04MeT) specifically prevents these lesions from causing G:C to A:T and A:T to G:C transition mutations, because if left unrepaired these lesions mispair during replication (1–6). On the other hand, the repair of N3-methylpurines (N3MeA and N3MeG) and 02-methylpyrimidines (02MeC and 02MeT) in E. coli specifically prevents cell killing (7–9). The repair of DNA alkylation damage in mammalian cells is somewhat less well understood, and it is not yet clear which alkylated lesions cause mutation and which cause cell death. Like E. coli, mammalian cells can repair 06alkylG, N3alkylA, N3alkylG, 04alkylT, 02alkylT and 02alkylC lesions (10–21). However, because observations have been made with a variety of cell types the results have not always been consistent. For instance, some studies indicated that 04MeT is repaired by rat liver cells (13,20,21), while others did not (22–24). Not all cell lines are able to repair all the alkylated lesions; for instance, CHO and V79 cells (25,26) and some human tumor cell lines (27–29) are unable to repair 06MeG. The ability of these particular cell lines to repair alkylated pyrimidines has not yet been measured. Other human cells, however, have been shown to repair 06MeG (19,27–29), 04alkylT, 02alkylT, 02alkylC (11), N3alkylA, N7alkylG (11,14,15), N3alkylG (15,30) and N7alkylA (15).

Keywords

Sister Chromatid Exchange Methyl Methane Sulfonate alkB Gene Alkylation Damage Sister Chromatid Exchange Induction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Leona Samson
    • 1
  • Patrick Carroll
    • 1
  • Bruce Derfler
    • 1
  • William Rebeck
    • 1
  1. 1.Charles A. Dana Laboratory of ToxicologyHarvard School of Public HealthBostonUSA

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