Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.350660
Title: Some chemical and biochemical studies relating to chemical carcinogens
Author: Russell, Jeremy Colin
ISNI:       0000 0001 3540 6682
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1984
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Abstract:
This thesis is largely concerned with the study of a series of compounds, related to 15,16-dihydrocyclopenta-[a]-phenanthren-17-one, which have very specific structure-activity relationships. Chapter 1 deals with the general tritiation of a number of these compounds, where labelling patterns were analysed using 3H-nmr spectroscopy. Similar studies were also performed on a related series of poly-aromatic hydrocarbons. The results of the detritiation kinetics,in aqueous sodium hydroxide, of a number of [16-[3]H]-15,16-dihydrocyclopenta-[a]-phenanthren-17-ones and similar ketones are presented in chapter 2. The results allowed interpretation in terms of both inductive effects and the three-dimensional shape of the molecules. Comparative in vitro metabolism of a number of 15,16-dihydrocyclopenta-[a]-phenanthren-17-ones, reported in chapter 3, showed that all of the compounds produce a trans-3,4-dihydrodiol in similar amounts, with the exception of the 1-methyl isomer, which yielded a 4-phenol. The mere presence of such a diol was shown not to necessarily imply carcinogenic activity in the compound under study. In chapter 4 the results of an investigation of the binding to DNA in vivo and in vitro of a series of 15,16-dihydrocyclopenta-[a]-phenanthren-17-ones are given. Each gave similar adduct patterns, where the major product is that derived from a deoxyguanosine residue. The dose/binding ratio of the 11-methyl derivative shows a linear relationship over a 32-fold range of dose, whilst the excision of the adducts from the DNA of the 12-methyl isomer is at a rate faster than that of cell division. The final chapter is concerned with the tritiation of a number of nitro and amino aromatic compounds, of interest in cancer chemistry. This was done either by direct catalytic exchange or by introducing the isotope as part of a synthetic step. The [3]H-nmr spectra of the products are presented.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.350660  DOI: Not available
Keywords: Biochemistry
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