Sensitivity of human cell strains having different abilities to repair O6-methylguanine in DNA to inactivation by alkylating agents including chloroethylnitrosoureas.

نویسندگان

  • D A Scudiero
  • S A Meyer
  • B E Clatterbuck
  • M R Mattern
  • C H Ziolkowski
  • R S Day
چکیده

In order to investigate the mechanisms of cellular damage by alkylating agents, human fibroblasts and tumor cell strains having different sensitivities to killing by N-methyl-N'-nitro-N-nitrosoguanidine [and different abilities to repair O6-methylguanine ( O6mGua ) in their DNA] were treated with other alkylating agents. Methyl methanesulfonate, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea, and N-ethyl-N'-nitro-N-nitrosoguanidine gave rise to sensitivity differences, but the differences were less than those observed with N-methyl-N'-nitro-N-nitrosoguanidine. After treatment with UV light, the strains showed similar survival. The data show that the DNA repair mechanism(s) responsible for the differential survival of the strains after N-methyl-N'-nitro-N-nitrosoguanidine treatment probably play(s) a role in repairing DNA damage produced by methyl methanesulfonate, N-ethyl-N'-nitro-N-nitrosoguanidine, BCNU, and 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea but not that produced by UV. Furthermore, the results support the idea that a breakdown product of BCNU, that does not cause damage repairable by O6mGua repair mechanisms, contributes to the lethal effects due to BCNU-produced DNA-damage that is repairable by O6mGua repair mechanisms. The survival data, along with nucleoid sedimentation and adenovirus host-cell reactivation data, are consistent with the hypothesis that the lesion(s) lethal to tumor cells defective in O6mGua DNA repair are lesions in which DNA oxygen atoms are alkylated.

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عنوان ژورنال:
  • Cancer research

دوره 44 6  شماره 

صفحات  -

تاریخ انتشار 1984