Xeroderma Pigmentosum Patients from Germany: Repair Capacity of 45 XP Fibroblast Strains of the Mannheim XP Collection As Measured by Colony-forming Ability and Unscheduled DNA Synthesis Following Treatment with Methyl Methanesulfonate And...

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 1986 Jan 1

PMID 3782263

Citations 6

Authors

H W Thielmann

L Edler

S Friemel

Affiliations

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Abstract

A total of 45 XP fibroblast strains from the Mannheim XP Collection (representatives of XP complementation groups A, C, D, E, F or G, I, and XP variants) were investigated for colony-forming ability (term: D0) after treatment with up to ten doses of the methylating carcinogen MeSO2OMe. As controls 16 fibroblast strains from normal donors were used. Except for 4 XP strains (1 from group C and 3 from group D) which, however, were borderline cases, none of the remaining 41 XP strains was found to be more sensitive than normal controls. This held true within the limits of an experimental accuracy (experimental variability of D0 values) of +/- 7%. When weighted means were calculated for XP complementation groups and compared with that of normal donors at a significance level of 5%, no significant difference was detected. In contrast, after exposure of 6 XP group D strains to MeNOUr, a weighted mean D0 value was obtained which was significantly decreased by 27%. Unscheduled DNA synthesis (term: G0 which serves as a measure of excision repair) after exposure to MeNOUr was quantitatively the same (experimental variability: +/- 8%) both in the group of normal strains and in most of the XP complementation groups. Exceptions were group E and group F (or G) which had higher, and group I which had lower repair. Analogous G0 values measured after exposure to MeSO2OMe (experimental variability: +/- 13%), however, differed from that of the control strains: they were lower in XP complementation groups A, D, E, F (or G), and I. However, groups A, E, F (or G), and I including only 3 individual strains or less may be considered to be possibly ill-represented. Yet, group D including 11 XP strains did show reduction of the mean G0 value by 35%. From this it is concluded that there are repair defects in XP group D strains with regard to MeSO2OMe-induced adducts. These defects seem to be small.

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References

Thielmann H, Edler L, Popanda O, Friemel S . Xeroderma pigmentosum patients from the Federal Republic of Germany: decrease in post-UV colony-forming ability in 30 xeroderma pigmentosum fibroblast strains is quantitatively correlated with a decrease in DNA-incising capacity. J Cancer Res Clin Oncol. 1985; 109(3):227-40. DOI: 10.1007/BF00390362. View

FISCHER E, Thielmann H, Neundorfer B, Rentsch F, Edler L, JUNG E . Xeroderma pigmentosum patients from Germany: clinical symptoms and DNA repair characteristics. Arch Dermatol Res. 1982; 274(3-4):229-47. DOI: 10.1007/BF00403726. View

Witte I, Thielmann H . Extracts of xeroderma pigmentosum group A fibroblasts introduce less nicks into methyl methanesulfonate-treated DNA than extracts of normal fibroblasts. Cancer Lett. 1979; 6(3):129-36. DOI: 10.1016/s0304-3835(79)80023-3. View

Lawley P, Orr D, Shah S, Farmer P, Jarman M . Reaction products from N-methyl-N-nitrosourea and deoxyribonucleic acid containing thymidine residues. Synthesis and identification of a new methylation product, O4-methylthymidine. Biochem J. 1973; 135(1):193-201. PMC: 1165804. DOI: 10.1042/bj1350193. View

ROBBINS J, Polinsky R, Moshell A . Evidence that lack of deoxyribonucleic acid repair causes death of neurons in xeroderma pigmentosum. Ann Neurol. 1983; 13(6):682-4. DOI: 10.1002/ana.410130621. View

Cleaver J . Defective repair replication of DNA in xeroderma pigmentosum. Nature. 1968; 218(5142):652-6. DOI: 10.1038/218652a0. View

Cleaver J . Xeroderma pigmentosum: a human disease in which an initial stage of DNA repair is defective. Proc Natl Acad Sci U S A. 1969; 63(2):428-35. PMC: 223582. DOI: 10.1073/pnas.63.2.428. View

Thielmann H, Popanda O, Edler L . XP patients from Germany: correlation of colony-forming ability, unscheduled DNA synthesis and single-strand breaks after UV damage in xeroderma pigmentosum fibroblasts. J Cancer Res Clin Oncol. 1982; 104(3):263-86. DOI: 10.1007/BF00406246. View

Thielmann H, FISCHER E, Dzarlieva R, Komitowski D, Popanda O, Edler L . Spontaneous in vitro malignant transformation in a xeroderma pigmentosum fibroblast line. Int J Cancer. 1983; 31(6):687-700. DOI: 10.1002/ijc.2910310603. View

10.

Pegg A . Methylation of the O6 position of guanine in DNA is the most likely initiating event in carcinogenesis by methylating agents. Cancer Invest. 1984; 2(3):223-31. DOI: 10.3109/07357908409104376. View

11.

Andrews A, Barrett S, ROBBINS J . Xeroderma pigmentosum neurological abnormalities correlate with colony-forming ability after ultraviolet radiation. Proc Natl Acad Sci U S A. 1978; 75(4):1984-8. PMC: 392467. DOI: 10.1073/pnas.75.4.1984. View

12.

Edler L, Groger P, Thielmann H . Computational statistics for cell survival curves. II. Evaluation of colony-forming ability of a group of cell strains by the APL function CFAGROUP. Comput Methods Programs Biomed. 1985; 21(1):47-54. DOI: 10.1016/0169-2607(85)90061-6. View

13.

ROBBINS J, Kraemer K, LUTZNER M, Festoff B, Coon H . Xeroderma pigmentosum. An inherited diseases with sun sensitivity, multiple cutaneous neoplasms, and abnormal DNA repair. Ann Intern Med. 1974; 80(2):221-48. DOI: 10.7326/0003-4819-80-2-221. View

14.

Kuhnlein U, Lee B, Penhoet E, Linn S . Xeroderma pigmentosum fibroblasts of the D group lack an apurinic DNA endonuclease species with a low apparent Km. Nucleic Acids Res. 1978; 5(3):951-60. PMC: 342035. DOI: 10.1093/nar/5.3.951. View

15.

Rydberg B, Lindahl T . Nonenzymatic methylation of DNA by the intracellular methyl group donor S-adenosyl-L-methionine is a potentially mutagenic reaction. EMBO J. 1982; 1(2):211-6. PMC: 553022. DOI: 10.1002/j.1460-2075.1982.tb01149.x. View

16.

Stich H, San R, Kawazoe Y . Increased sensitivity of xeroderma pigmentosum cells to some chemical carcinogens and mutagens. Mutat Res. 1973; 17(1):127-37. DOI: 10.1016/0027-5107(73)90261-3. View

17.

Friedberg E, Anderson C, Bonura T, Cone R, Radany E, Reynolds R . Recent developments in the enzymology of excision repair of DNA. Prog Nucleic Acid Res Mol Biol. 1981; 26:197-215. DOI: 10.1016/s0079-6603(08)60405-5. View

18.

Setlow R, Regan J, German J, Carrier W . Evidence that xeroderma pigmentosum cells do not perform the first step in the repair of ultraviolet damage to their DNA. Proc Natl Acad Sci U S A. 1969; 64(3):1035-41. PMC: 223340. DOI: 10.1073/pnas.64.3.1035. View

19.

Swann P, MAGEE P . Nitrosamine-induced carcinogenesis. The alklylation of nucleic acids of the rat by N-methyl-N-nitrosourea, dimethylnitrosamine, dimethyl sulphate and methyl methanesulphonate. Biochem J. 1968; 110(1):39-47. PMC: 1187106. DOI: 10.1042/bj1100039. View

20.

FISCHER E, Keijzer W, Thielmann H, Popanda O, Bohnert E, Edler L . A ninth complementation group in xeroderma pigmentosum, XP I. Mutat Res. 1985; 145(3):217-25. DOI: 10.1016/0167-8817(85)90030-6. View