O6-methylguanine and temozolomide can reverse the resistance to chloroethylnitrosoureas of a mouse L1210 leukemia

M. D'Incalci, P. Taverna, E. Erba, S. Filippeschi, D. Potenza, L. Mariani, L. Citti, C. V. Catapano

Research output: Contribution to journalArticlepeer-review

Abstract

Using L1210 and a subline resistance to chloroethylnitrosoureas (L1210/BCNU), we found that the resistance to 1-(2-chloroethyl)-1-nitrosourea (CNU) or to diethyl-1-3-(2-chloroethyl)-3-nitrosoureido ethyl phosphonate (fotemustine) can be reversed by a pretreatment with O6-methyl Guanine (O6-mGua) or temozolomide. In L1210/BCNU but not in L1210 the pretreatment with O6mGua caused an increased peak level of CNU-induced DNA-interstrand crosslinks. We then evaluated whether the resistance to BCNU could be counteracted in vivo by i.p. O6mGua treatment of L1210/BCNU bearing mice. The results were negative due to the fact that O6mGua, which was not toxic when given alone, caused a high toxicity when associated with BCNU.

Original languageEnglish
Pages (from-to)115-121
Number of pages7
JournalAnticancer Research
Volume11
Issue number1
Publication statusPublished - 1991

Keywords

  • nitrosoureas
  • O-alkylguanine DNA alkyl transferase
  • O-methylguanine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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