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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).

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Hematoporphyrin Derivative - Photosensitized Dna Damage :/
Reminder of title:	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).
Author:	Blazek, Ed Robert.
Description:	1 online resource (593 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 46-07, Section: B.
Contained By:	Dissertations Abstracts International46-07B.
Subject:	Biophysics. -
Online resource:	click for full text (PQDT)
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). - 1 online resource (593 pages)

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

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

Includes bibliographical references

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.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9798205563772Subjects--Topical Terms:

581576
Biophysics.
Index Terms--Genre/Form:

554714
Electronic books.

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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245 1 0 $a Hematoporphyrin Derivative - Photosensitized Dna Damage : $b 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).
264 0 $c 1985
300 $a 1 online resource (593 pages)
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338 $a online resource $b cr $2 rdacarrier
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.
504 $a Includes bibliographical references
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.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2024
538 $a Mode of access: World Wide Web
650 4 $a Biophysics. $3 581576
655 7 $a Electronic books. $2 local $3 554714
690 $a 0786
710 2 $a ProQuest Information and Learning Co. $3 1178819
710 2 $a State University of New York at Buffalo. $3 1098740
773 0 $t Dissertations Abstracts International $g 46-07B.
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=8528235 $z click for full text (PQDT)