Process for identifying compounds which protect against the form

Details Process for identifying compounds which protect against the form Process for identifying compounds which protect against the form

1997-05-07

2000-01-25

Gitomer, Ralph

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving nucleic acid

435 34, 436811, C12Q 168

Patent

active

060177063

ABSTRACT:
Processes for detecting compounds which protect against fluorescent light-induced DNA lesions, in particular DNA lesions which are induced by oxygen free radicals, are disclosed. The methods of the present invention encompass modifying G.sub.1 -phase test and/or G.sub.2 -phase tests so that a compound which is suspected of being capable of protecting against the formation of fluorescent light-induced DNA lesions (i.e., a suspected "DNA protectant"), such as an anti-oxidant or free-radical scavenger, is added to the cell cultures prior to irradiation of the cell cultures with fluorescent light or x-rays. Addition of a DNA protectant to cultures of human skin fibroblasts or PHA-stimulated blood lymphocytes significantly reduces the frequency of radiation-induced chromatid breaks so that there is a small, preferably no, statistical difference in the frequency of radiation-induced chromatid breaks in Alzheimer disease cells in the presence or absence of caffeine in the G.sub.1 -phase test using fluorescent light, or in normal cells in the presence or absence of ara-C in the G.sub.2 -phase test using fluorescent light or x-rays.

REFERENCES:
patent: 4933274 (1990-06-01), Sanford et al.
patent: 4975365 (1990-12-01), Grossman et al.
patent: 5482833 (1996-01-01), Pero et al.
patent: 5641754 (1997-06-01), Iversen
patent: 5773219 (1998-06-01), Sanford-Mifflin et al.
Parshad, R., Price, F. Tarone, R.J. Robbins and Sanford, K.K. (1991) "Cytogenetic evidence of a cell-cycle-dependent DNA repair deficiency: A possible diagnostic feature of Alzheimer Disease." Proceedings of the 8th International Congress of Human Genetics, Oct. 6-11, 1991, Washington, D.C. U.S.A., Am. J. Human Genetics Suppl. 49, 155. Abstract.
Chen, P., et al., "Heterogeneity in Alzheimer's disease: evidence from cellular radiosensitivity and complementation of this phenotype", Mutation Res. (1991) 256, 21-7.
Tobi, S.E., et al. "Chromosomal radiosensitivity of lymphocytes from Alzheimer's disease patents", J. Med. Genet. (1990) 437-40.
Parshad, R., et al., "Susceptibility to fluorescent light-induced chromatid breaks associated with DNA repair deficiency and malignant transformation in culture", Cancer Res. (1980) 40, 4415-9.
Price, F.M., et al., "Radiation-induced chromatid aberrations in Cockayne syndrome and xeroderma pigmentosum group C fibroblasts in relation to cancer predisposition", Cancer Genet. Cytogenet. (1991) 57, 1-10.
Sanford, K.K., et al., "Responses of human cells in culture to hydrogen peroxide and related free radicals generated by visible light: relationship to cancer susceptiblity", in Free Radicals, Aging, and Degenerative Diseases, edited by Johnson, J.E., et al., Alan R. Liss, Inc., New York, 1986, pp. 373-394.
Sanford, K.K., et al., "Role of DNA repair in malignant neoplastic transformation of human mammary epithelial cells in culture", Carcinogenesis (1992) 13, 1137-41.
Parshad, R., et al., "Neoplastic Transformation of human cells in culture associated with deficient repair of light-induced chromosomal DNA damage", Int. J. Cancer: 30, 153-159 (1982).
Parshad, R., et al., "Chromatid damage induced by fluorescent light during G.sub.2 phase in normal and Gardner Syndrome fibroblasts," Interpretation in terms of deficient DNA repair, Mutation Research, 151 (1985) 57-63.
Gantt R., et al., "Enhanced G.sub.2 chromatid radiosensitivity, an early stage in the neoplastic transformation of human epidermal keratinocytes in culture", Cancer Research 47, 1390-1397 (1987).
Parshad, R., et al., A DNA-Repair Defect In Alzheimer Disease, vol. 42, No. 1, 98A (1994) (Abstracts Submitted to the Annual Meeting of the Western Section of the American Federation for Clinical Research held Feb. 9-12, (1994) (published after filing date of first priority application) Abstract.
Melnick, L., et al., "Defective DNA Repair In Alzheimer Disease: Use In A Predictive Test On Cultured Cell Lines", Clinical Research vol. 42, No. 3, 464A (Oct. 1994) (published after filing dates of first two priority applications) Ab.
Parshad, R., et al., "Defective DNA Repair In Sporadic, Familial, And Down-Syndrome Alzheimer Disease", Journal of Investigative Medicine, vol. 43 (Supplement 2), 415A (Apr. 1995) (published after filing dates of first two priority applications).
Melnick, L.K., et al., "Xeroderma Pigmentosum Group-A And Alzheimer Disease Cells Have Similar Defective Repair of Fluorescent Light-Induced DNA Damage", Journal of Investigative Medicine, vol. 43 (Supplement 3), 508A, (Sep. 1995) (published after filing dates of first two priority applications).
Backon, J., "Dementia in Cancer Patients Undergoing Chemotherapy: Implication of Free Radical Injury and Relevance to Alzheimer Disease", Medical Hypotheses, 35, 146-147 (1991).
Parshad, R., Sanford, K.K., Price. F.M., Melnick, L.K., Nee, L.E., Schapiro, M.B., Tarone, R.E. and Robbins, J.H. "Fluorescent light-induced chromatid breaks distinguish Alzheimer disease cells from normal cells in tissue culture", Proc. Natl. Acad. Sci., USA 93, 5146-5150 (May 1996) (published after the filing dates of the three priority applications).
"Paradigm of DNA-Repair Disease, Points To Alzheimer's Diagnosis, Therapy", BioWorld Today, vol. 7, No. 102, 1-2, (May 23, 1996) (published after the filing dates of the three priority applications).
Parshad R., Neoplastic Transformation of Human Cells in Culture Associated with Deficient Repair of Light Induced Chromosomal DNA Damage, Int J Cancer 30 153-159, 1982.
Pincheira J., G2 Repair and Evaluation of the Cytogenetic Damage Induced by Low Doses of X-Irradiation During G0 in Human Lymphocytes, Biol Res 28(4):267-275, 1995.
Parchad R., Fluorescent Light-Induced Chromatid Breaks Distinguish Alzheimer Disease Cells From Normal Cells in Tissue Culture, Proc. Natl. Acad. Sci. USA 93:51466-5150, May 1996.
Antoccia A., Chromosomal Sensitivity to Clastogenic Agents and Cell Cycle Perturbations in Nijmegen Breakage Syndrome Lymphoblastoid Cell Lines, Int J Radiat Biol 71(1):41-49, 1997.

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