MQ62942 - The Direct Study of the Reaction of the Tamoxifen...

Info iconThis preview shows pages 1–6. Sign up to view the full content.

View Full Document Right Arrow Icon
The Direct Study of the Reaction the Tamoxifen Carbocation with DNA George Marji A thesis submitted in conformity with the requirements for the degree of Master of Science Graduate Department of Chemistry University of Toronto O Copyright by George Marji (100 1)
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
National Library 1*1 of Cm& Biiiothbque nationale du Canada Acquisitions and Acquisitions et Bibliographie Seivices services bibliographiques 395 Wellington Street 395. nut Wellingt6n OnawaON KlAON4 WON canada CaMda The author has granteci a non- L'auteur a accordé une licence non exclusive licence allowing the exclusive permettant à la Canada to Bibliothèque nationale du de reproduce, loan, distri'bute or seiî reproduire, prêter, distribuer ou copies of this thesis in microform, vendre des copies de cette thèse sous paper or electronic formats. forme de microfiche/frlm, reproduction sur papier ou format électronique. The author retains ownership the conserve propriété copyright thesis. Neither droit d'auteur qui protège cette thèse. nor substantial extracts firom it Ni îhèse ni des extraits substantiels may be printed or otherwise de celle-ci ne doivent être imprimés reproduced without author's ou autrement reproduits sans son pehssion. autorisation.
Background image of page 2
For Mom and Dad
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
The Direct Study of the Reaction of Tamoxifen Carbocation with DNA Master of Science. 200 1 George Marji Graduate Department of Chemistry University of Toronto Abstract Of the women adrninistered tamoxifen (TM to treat breast cancer. a small percentage developed endometrial adenocarcinornas. The rnechanism of carcinogenesis intolves the formation of a carbocation intermediate (T.4M3 that binds IO cellular DNA causing frarneshifi mutations. To examine the binding that leads to the formation of adducts. a detailed study of TAiM in the presence of DNA was conducted. TAM- was showm. by kinetic rneasurements. to form non-covalent association complexes with DNA. This electrostatic binding was confirmed by varying pH and ionic strength. Decreasing pH and added salt increased the binding constant and observed rates. The TAM-*DNA complex reacts with water and DNA to tom alcohols and adducts respective{';. The sçlectivity ratios (rate of reaction with DNA vs. water) were: by HPLC. 7.3 1 x 10' M-' and 3.75 x M" at 22°C and 37'C respectively; by laser flash photolysis, 7.76 x IO" M-' and 1.86 x 10' M-' at 22'C and 37'C respectively. DNA is a better nucleophile than polyguanylic acid or deoxyguanosine alone.
Background image of page 4
Acknowledgements First and foremost. I'd like to thank my supervisor and teacher. Robert McClelland, for your expertise and leadership. Your presence and enthusiasm in the lab was inspirationa!. and 1 am gatefÙ1 for the opportunity to have worked with you on this exciting research project. 1 would also like to Cristina Sinchez for gening the bal1 rolling on this project.
Background image of page 5

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 6
This is the end of the preview. Sign up to access the rest of the document.

This note was uploaded on 08/12/2009 for the course IQ 23123 taught by Professor Varios during the Spring '09 term at Universidade de Brasília.

Page1 / 102

MQ62942 - The Direct Study of the Reaction of the Tamoxifen...

This preview shows document pages 1 - 6. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online