Adaptive increase of O6-methlguanine-acceptor protein in HeLa cells following N-methyl-N′-nitro-N-nitrosoguanidine treatment
- 1 January 1982
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 10 (15) , 4595-4604
- https://doi.org/10.1093/nar/10.15.4595
Abstract
We have assayed in extracts of HeLa cells the amount of acceptor protein that removes O6-methylguanine adducts from alkylated DNA. Cells were treated with single or multiple nontoxic doses of N-methyl-N'-nitrosoguanidine (MNNG) and the extracts were analyzed up to 32 h after the last exposure. The acceptor activity assayed immediately (1 h) after single exposures decreases linearly with dose indicating that the acceptor protein is used up by endogenous O6-methylguanine adducts in a stoichiometric reaction. Multiple exposures, assayed 8-24 h after the last exposure, increase the amount of acceptor protein in a dose dependent fashion followed by a decrease above a cumulative dose of 100 ng/ml. Under conditions of maximum induction, there are about 300,000 acceptor protein sites per cell, approximately 3 fold above the constitutive level. Both in adapted and unadapted cells the methyl group from O6-methylguanine adducts in the alkylated DNA is transferred to cysteine residues of the acceptor protein(s).Keywords
This publication has 31 references indexed in Scilit:
- Pretreatment with acetylaminofluorene enhances the repair of O6-methylguanine in DNANature, 1979
- Quantitation of the adaptive response to alkylating agentsNature, 1979
- N-Nitroso Alkylating Agents: Formation and Persistence of Alkyl Derivatives in Mammalian Nucleic Acids as Contributing Factors in Carcinogenesis5JNCI Journal of the National Cancer Institute, 1979
- The stability of methylated purines and of methylphosphotriesters in the DNA of V79 cells after treatment with N-methyl-N-nitrosoureaBiochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1979
- INCREASED EXCISION OF O6-METHYLGUANINE FROM RAT-LIVER DNA AFTER CHRONIC ADMINISTRATION OF DIMETHYLNITROSAMINE1979
- Repair of O6-methylguanine in adapted Escherichia coli.Proceedings of the National Academy of Sciences, 1978
- Dimethylnitrosamine inhibits enzymatic removal of O6-methylguanine from DNANature, 1978
- DNA alkylation and neuro-oncogenesis by 3,3-dimethyl-1-phenyltriazeneActa Neuropathologica, 1978
- A new pathway for DNA repair in Escherichia coliNature, 1977
- Mammalian cell cycle analysis using microspectrophotometry combined with autoradiographyExperimental Cell Research, 1965