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

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

Istituto di Ricerche Farmacologiche "Mario Negri"

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	115-121
Number of pages	7
Journal	Anticancer Research
Volume	11
Issue number	1
Publication status	Published - 1991

Keywords

nitrosoureas
O-alkylguanine DNA alkyl transferase
O-methylguanine

ASJC Scopus subject areas

Cancer Research
Oncology

Cite this

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

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.",

keywords = "nitrosoureas, O-alkylguanine DNA alkyl transferase, O-methylguanine",

author = "M. D'Incalci and P. Taverna and E. Erba and S. Filippeschi and D. Potenza and L. Mariani and L. Citti and Catapano, {C. V.}",

year = "1991",

language = "English",

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TY - JOUR

T1 - O6-methylguanine and temozolomide can reverse the resistance to chloroethylnitrosoureas of a mouse L1210 leukemia

AU - D'Incalci, M.

AU - Taverna, P.

AU - Erba, E.

AU - Filippeschi, S.

AU - Potenza, D.

AU - Mariani, L.

AU - Citti, L.

AU - Catapano, C. V.

PY - 1991

Y1 - 1991

N2 - 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.

AB - 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.

KW - nitrosoureas

KW - O-alkylguanine DNA alkyl transferase

KW - O-methylguanine

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JO - Anticancer Research

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

Abstract

Keywords

ASJC Scopus subject areas

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