Abstract
Extracts of peripheral lymphocytes from six individuals with chronic lymphocytic leukemia (CLL) were assayed for the ability to remove O6-methylguanine (O6MeGua) from exogenous DNA. The O6MeGua-removing activity in CLL lymphocytes, predominantly B cells, was approximately 7-fold higher than in B lymphocytes of normal individuals and about 2-fold higher than in the unstimulated T type cells of normal persons. The activity measured in extracts of lymphocytes from three blood relatives was in the upper range of the normal distribution. Over 80% of the removal of O6MeGua was accomplished by the transfer of the methyl group to cysteine moieties of acceptor proteins in a stoichiometric reaction. If one assumes one acceptor group per acceptor protein, the calculated number of acceptor molecules per CLL lymphocyte falls between 91,000 and 220,000. Thus CLL lymphocytes do not show lower O6MeGua-removing activity, in contrast to many tumor cell strains or transformed cell lines, which are reported to have a deficient methyl excision repair phenotype (Mer-). Instead, the CLL lymphocytes act as if they have a super-Mer+ phenotype.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bogden J. M., Eastman A., Bresnick E. A system in mouse liver for the repair of O6-methylguanine lesions in methylated DNA. Nucleic Acids Res. 1981 Jul 10;9(13):3089–3103. doi: 10.1093/nar/9.13.3089. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Day R. S., 3rd, Ziolkowski C. H., Scudiero D. A., Meyer S. A., Lubiniecki A. S., Girardi A. J., Galloway S. M., Bynum G. D. Defective repair of alkylated DNA by human tumour and SV40-transformed human cell strains. Nature. 1980 Dec 25;288(5792):724–727. doi: 10.1038/288724a0. [DOI] [PubMed] [Google Scholar]
- Harris G., Lawley P. D., Olsen I. Mode of action of methylating carcinogens: comparative studies of murine and human cells. Carcinogenesis. 1981;2(5):403–411. doi: 10.1093/carcin/2.5.403. [DOI] [PubMed] [Google Scholar]
- Huang A. T., Kremer W. B., Laszlo J., Setlow R. B. DNA repair in human leukaemic lymphocytes. Nat New Biol. 1972 Nov 22;240(99):114–116. doi: 10.1038/newbio240114a0. [DOI] [PubMed] [Google Scholar]
- Karran P., Lindahl T., Griffin B. Adaptive response to alkylating agents involves alteration in situ of O6-methylguanine residues in DNA. Nature. 1979 Jul 5;280(5717):76–77. doi: 10.1038/280076a0. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Medcalf A. S., Lawley P. D. Time course of O6-methylguanine removal from DNA of N-methyl-N-nitrosourea-treated human fibroblasts. Nature. 1981 Feb 26;289(5800):796–798. doi: 10.1038/289796a0. [DOI] [PubMed] [Google Scholar]
- Mehta J. R., Ludlum D. B., Renard A., Verly W. G. Repair of O6-ethylguanine in DNA by a chromatin fraction from rat liver: transfer of the ethyl group to an acceptor protein. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6766–6770. doi: 10.1073/pnas.78.11.6766. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mogensen C. E. The glomerular permeability determined by dextran clearance using Sephadex gel filtration. Scand J Clin Lab Invest. 1968;21(1):77–82. doi: 10.3109/00365516809076979. [DOI] [PubMed] [Google Scholar]
- Montesano R., Brésil H., Margison G. P. Increased excision of O6-methylguanine from rat liver DNA after chronic administration of dimethylnitrosamine. Cancer Res. 1979 May;39(5):1798–1802. [PubMed] [Google Scholar]
- Olsson M., Lindahl T. Repair of alkylated DNA in Escherichia coli. Methyl group transfer from O6-methylguanine to a protein cysteine residue. J Biol Chem. 1980 Nov 25;255(22):10569–10571. [PubMed] [Google Scholar]
- Rai K. R., Sawitsky A., Cronkite E. P., Chanana A. D., Levy R. N., Pasternack B. S. Clinical staging of chronic lymphocytic leukemia. Blood. 1975 Aug;46(2):219–234. [PubMed] [Google Scholar]
- Ringborg U., Lambert B. Ultraviolet-induced DNA-repair synthesis in lymphocytes from patients with chronic lymphatic leukemia. Cancer Lett. 1977 Jul;3(1-2):77–81. doi: 10.1016/s0304-3835(77)94333-6. [DOI] [PubMed] [Google Scholar]
- Samson L., Cairns J. A new pathway for DNA repair in Escherichia coli. Nature. 1977 May 19;267(5608):281–283. doi: 10.1038/267281a0. [DOI] [PubMed] [Google Scholar]
- Shiloh Y., Becker Y. Kinetics of O6-methylguanine repair in human normal and ataxia telangiectasia cell lines and correlation of repair capacity with cellular sensitivity to methylating agents. Cancer Res. 1981 Dec;41(12 Pt 1):5114–5120. [PubMed] [Google Scholar]
- Singer B. N-nitroso alkylating agents: formation and persistence of alkyl derivatives in mammalian nucleic acids as contributing factors in carcinogenesis. J Natl Cancer Inst. 1979 Jun;62(6):1329–1339. [PubMed] [Google Scholar]
- Sklar R., Strauss B. Removal of O6-methylguanine from DNA of normal and xeroderma pigmentosum-derived lymphoblastoid lines. Nature. 1981 Jan 29;289(5796):417–420. doi: 10.1038/289417a0. [DOI] [PubMed] [Google Scholar]
