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HEMATOPORPHYRIN DERIVATIVE - PHOTOSE...

BLAZEK, ED ROBERT.

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HEMATOPORPHYRIN DERIVATIVE - PHOTOSENSITIZED DNA DAMAGE: HYDRODYNAMIC STUDIES IN MAMMALIAN CELL CULTURE VS. SPECTROSCOPIC STUDIES IN A DINUCLEOSIDE MONOPHOSPHATE MODEL COMPOUND (ALKALINE ELUTION, NMR, CHINESE HAMSTER OVARY K1, 2'-DEOXYCYTIDYLYL(3'-5')2'-DEOXYGUANOSINE, PROTEIN COVALENT CROSSLINKS).

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	HEMATOPORPHYRIN DERIVATIVE - PHOTOSENSITIZED DNA DAMAGE: HYDRODYNAMIC STUDIES IN MAMMALIAN CELL CULTURE VS. SPECTROSCOPIC STUDIES IN A DINUCLEOSIDE MONOPHOSPHATE MODEL COMPOUND (ALKALINE ELUTION, NMR, CHINESE HAMSTER OVARY K1, 2'-DEOXYCYTIDYLYL(3'-5')2'-DEOXYGUANOSINE, PROTEIN COVALENT CROSSLINKS)./
作者:	BLAZEK, ED ROBERT.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 1985,
面頁冊數:	593 p.
附註:	Source: Dissertations Abstracts International, Volume: 46-07, Section: B.
Contained By:	Dissertations Abstracts International46-07B.
標題:	Biophysics. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=8528235
ISBN:	9798205563772

HEMATOPORPHYRIN DERIVATIVE - PHOTOSENSITIZED DNA DAMAGE: HYDRODYNAMIC STUDIES IN MAMMALIAN CELL CULTURE VS. SPECTROSCOPIC STUDIES IN A DINUCLEOSIDE MONOPHOSPHATE MODEL COMPOUND (ALKALINE ELUTION, NMR, CHINESE HAMSTER OVARY K1, 2'-DEOXYCYTIDYLYL(3'-5')2'-DEOXYGUANOSINE, PROTEIN COVALENT CROSSLINKS).
BLAZEK, ED ROBERT.

HEMATOPORPHYRIN DERIVATIVE - PHOTOSENSITIZED DNA DAMAGE: HYDRODYNAMIC STUDIES IN MAMMALIAN CELL CULTURE VS. SPECTROSCOPIC STUDIES IN A DINUCLEOSIDE MONOPHOSPHATE MODEL COMPOUND (ALKALINE ELUTION, NMR, CHINESE HAMSTER OVARY K1, 2'-DEOXYCYTIDYLYL(3'-5')2'-DEOXYGUANOSINE, PROTEIN COVALENT CROSSLINKS). - Ann Arbor : ProQuest Dissertations & Theses, 1985 - 593 p.

Source: Dissertations Abstracts International, Volume: 46-07, Section: B.

Thesis (Ph.D.)--State University of New York at Buffalo, 1985.

This item must not be sold to any third party vendors.

DNA damage produced by visible light and the tumor localizer-photosensitizer hematoporphyrin derivative (HPD) was studied in Chinese hamster ovary cells using alkaline elution, a sensitive hydrodynamic assay, and in aerated aqueous solution of the DNA model compound 2'-deoxycytidylyl(3'-5')-2'-deoxyguanosine d(CpG) by chromatographic isolation of damage products followed by ultraviolet absorbance and nuclear magnetic resonance spectroscopy, mass spectrometry, and enzymatic digestion. Alkaline elution of photosensitized cellular DNA revealed a complex spectrum of damage types, including (1) sites which are frank breaks or are converted to breaks within 90 min at pH 12.1; (2) additional breaks which appear within 90 min at pH 12.6; (3) sites which appear hypersensitive to subsequent breakage by x-radiation; (4) covalent DNA-protein crosslinks (DPCs); and (5) alkali-labile (AL) sites which break throughout the elution period at pH 12.6. These AL sites are contingent upon a period of repair incubation for the treated cell; 15 min permits their full expression. They are not cleaved by the apurinic-apyrimidinic endonuclease activity of E. coli exonuclease III, and undergo no measurable repair during 3 h of incubation. Type 1 sites are repaired more slowly than are strand breaks due to x-radiation, and their repair is more vulnerable to certain enzymatic inhibitors than is the repair of x-ray induced breaks. Type 2 sites are repaired, after a delay, between the second and third hours following photosensitization. Type 3 sites are repaired steadily within 3 h. Measurements of the repair rate of DPCs have given conflicting results ranging from total repair within 3 h to no repair within 8 h. HPD photosensitization of d(CpG) yielded at least 38 products; six of the most abundant were purified. Guanine H8 was undetectable by ('1)H-NMR for all six products in D(,2)O solution. The imino (1-NH) resonance of four products was unobservable in DMSO-d(,6). Five products remained dinulceoside monophosphates with damage confined to the guanine base; one product suffered only cleavage of the glycosidic bond, leaving the abasic sugar primarily in its (alpha)-anomeric form. Substantial differences between HPD-photosensitized and ionizing radiation-induced DNA damage are manifest at both macromolecular and molecular scales. These differences invalidate early arguments that DNA damage cannot be important to the in vitro cytotoxicity of porphyrin photosensitization.

ISBN: 9798205563772Subjects--Topical Terms:

518360
Biophysics.

HEMATOPORPHYRIN DERIVATIVE - PHOTOSENSITIZED DNA DAMAGE: HYDRODYNAMIC STUDIES IN MAMMALIAN CELL CULTURE VS. SPECTROSCOPIC STUDIES IN A DINUCLEOSIDE MONOPHOSPHATE MODEL COMPOUND (ALKALINE ELUTION, NMR, CHINESE HAMSTER OVARY K1, 2'-DEOXYCYTIDYLYL(3'-5')2'-DEOXYGUANOSINE, PROTEIN COVALENT CROSSLINKS).
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100 1 $a BLAZEK, ED ROBERT. $3 3763694
245 1 0 $a HEMATOPORPHYRIN DERIVATIVE - PHOTOSENSITIZED DNA DAMAGE: HYDRODYNAMIC STUDIES IN MAMMALIAN CELL CULTURE VS. SPECTROSCOPIC STUDIES IN A DINUCLEOSIDE MONOPHOSPHATE MODEL COMPOUND (ALKALINE ELUTION, NMR, CHINESE HAMSTER OVARY K1, 2'-DEOXYCYTIDYLYL(3'-5')2'-DEOXYGUANOSINE, PROTEIN COVALENT CROSSLINKS).
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300 $a 593 p.
500 $a Source: Dissertations Abstracts International, Volume: 46-07, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
502 $a Thesis (Ph.D.)--State University of New York at Buffalo, 1985.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
520 $a DNA damage produced by visible light and the tumor localizer-photosensitizer hematoporphyrin derivative (HPD) was studied in Chinese hamster ovary cells using alkaline elution, a sensitive hydrodynamic assay, and in aerated aqueous solution of the DNA model compound 2'-deoxycytidylyl(3'-5')-2'-deoxyguanosine d(CpG) by chromatographic isolation of damage products followed by ultraviolet absorbance and nuclear magnetic resonance spectroscopy, mass spectrometry, and enzymatic digestion. Alkaline elution of photosensitized cellular DNA revealed a complex spectrum of damage types, including (1) sites which are frank breaks or are converted to breaks within 90 min at pH 12.1; (2) additional breaks which appear within 90 min at pH 12.6; (3) sites which appear hypersensitive to subsequent breakage by x-radiation; (4) covalent DNA-protein crosslinks (DPCs); and (5) alkali-labile (AL) sites which break throughout the elution period at pH 12.6. These AL sites are contingent upon a period of repair incubation for the treated cell; 15 min permits their full expression. They are not cleaved by the apurinic-apyrimidinic endonuclease activity of E. coli exonuclease III, and undergo no measurable repair during 3 h of incubation. Type 1 sites are repaired more slowly than are strand breaks due to x-radiation, and their repair is more vulnerable to certain enzymatic inhibitors than is the repair of x-ray induced breaks. Type 2 sites are repaired, after a delay, between the second and third hours following photosensitization. Type 3 sites are repaired steadily within 3 h. Measurements of the repair rate of DPCs have given conflicting results ranging from total repair within 3 h to no repair within 8 h. HPD photosensitization of d(CpG) yielded at least 38 products; six of the most abundant were purified. Guanine H8 was undetectable by ('1)H-NMR for all six products in D(,2)O solution. The imino (1-NH) resonance of four products was unobservable in DMSO-d(,6). Five products remained dinulceoside monophosphates with damage confined to the guanine base; one product suffered only cleavage of the glycosidic bond, leaving the abasic sugar primarily in its (alpha)-anomeric form. Substantial differences between HPD-photosensitized and ionizing radiation-induced DNA damage are manifest at both macromolecular and molecular scales. These differences invalidate early arguments that DNA damage cannot be important to the in vitro cytotoxicity of porphyrin photosensitization.
590 $a School code: 0656.
650 4 $a Biophysics. $3 518360
690 $a 0786
710 2 $a State University of New York at Buffalo. $3 1017814
773 0 $t Dissertations Abstracts International $g 46-07B.
790 $a 0656
791 $a Ph.D.
792 $a 1985
793 $a English
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=8528235