P.L. Grover
Institute of Cancer Research
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Featured researches published by P.L. Grover.
Chemico-Biological Interactions | 1978
Brian Tierney; B. Abercrombie; Christine Walsh; Alan Hewer; P.L. Grover; Peter J. Sims
The products formed when the carcinogenic polycyclic hydrocarbon 7-methylbenz[a] anthracene is oxidized with an ascorbic acid-ferrous sulphate mixture have been investigated. All 5 possible dihydrodiols were formed and the isolation of the 3 non-K-region dihydrodiols, trans-1,2-dihydro-1,2-dihydroxy-7-methylbenz[a]anthracene, trans-3,4-dihydro-3,4-dihydroxy-7-methylbenz[a] anthracene and trans-8,9-dihydro-8,9-dihydroxy-7-methylbenz[a] anthracene is described. The purification of the dihydrodiols was carried out by thin-layer (TLC) followed by preparative high pressure liquid chromatography (HPLC). The ultra-violet, spectral and nuclear magnetic resonance (NMR) characteristics of the dihydrodiols are reported and the data used to assign the proposed structures. An explanation for the unusual preferred conformation which the 8,9-dihydrodiol adopts is advanced.
Cancer Letters | 1985
P. Vigny; A. Brunissen; David H. Phillips; Colin S. Cooper; Alan Hewer; P.L. Grover; Peter J. Sims
The hydrocarbon-deoxyribonucleoside adducts present in DNA isolated from the mammary glands of rats that had been treated with 7,12-dimethylbenz[a]anthracene (DMBA) were separated by Sephadex LH20 column chromatography, purified by high performance liquid chromatography (HPLC), and examined by photon-counting spectrophotofluorimetry. The adducts were found to have anthracene-like fluorescence spectra which is consistent with the reaction of diol-epoxides formed in the 1,2,3,4-ring of DMBA with mammary gland DNA.
Cancer Letters | 1992
W Pfau; N C Hughes; P.L. Grover; David H. Phillips
Analysis using 32P-postlabelling and a recently developed HPLC method resolved the adduct formed by reaction of the benzo[b]fluoranthene (BbF) anti-bay-region diol-epoxide with DNA from the more polar major adduct produced by the hydrocarbon in three different biological systems. In each case, the adduct formed from the anti-bay-region diol-epoxide constituted only a minor proportion of the total DNA modification. Comparisons of the DNA adducts formed from the hydrocarbon with those formed in microsomal incubations from the putative metabolites BbF-9,10-diol, anti-BbF-9,10-diol-11,12-oxide and the 5,9,10- and 6,9,10-BbF-triols indicate that the predominant pathway for BbF activation in skin probably involves a bay-region triol-epoxide possessing a phenolic OH-group on the peninsula ring.
Chemico-Biological Interactions | 1979
Alan Hewer; Odartey Ribeiro; Christine Walsh; P.L. Grover; Peter J. Sims
In the oxidation of benzo[alpha]pyrene in an abscorbic acid-ferrous sulphate-EDTA system, four dihydrodiols were detected. Three, trans-4,5-dihydro-4,5-dihydroxybenzo[alpha]pyrene, trans-7,8-dihydro-7,8-dihydroxybenzo[alpha]pyrene and trans-9,10-dihydro-9,10-dihydroxybenzo[alpha]pyrene were identified by their UV spectra and by direct comparisons of their chromatographic properties, using HPLC, with those of the authentic compounds. The fourth compound appeared to be trans-11,12-dihydro-11,12-dihydroxybenzo[alpha]pyrene since its ultraviolet spectrum was identical to that of the cis-dihydrodiol. Time-course experiments showed that the maximum amounts of products were obtained after 8 h of oxidation. A re-examination of the dihydrodiols formed from benzo[alpha]pyrene by rat-liver microsomal fractions failed to show the formation of the trans-11,12-dihydrodiol.
Cancer Letters | 1983
I. Chouroulinkov; H. Coulomb; Alan D. MacNicoll; P.L. Grover; Peter J. Sims
The tumor-initiating activities of dibenz[a,c]anthracene (DBA) and of the related trans-1,2-, 3,4- and 10,11-dihydrodiols have been examined on mouse skin subsequently promoted with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The 1,2- and 10,11-dihydrodiols were active and were more active than equivalent doses of either the parent hydrocarbon or the 3,4-dihydrodiol. The data are discussed in relation to possible mechanisms that may be involved in the metabolic activation of DBA.
Cancer Letters | 1991
S. Lecoq; M. NíShé; P.L. Grover; Karl-Ludwig Platt; Franz Oesch; David H. Phillips
DNA has been incubated in vitro with dibenz[a,h]anthracene (DB[a,H]A) and the related 5,6-diol and 3,4-diol in the presence of 3-methylcholanthrene- or Aroclor 1254-induced rat liver microsomes. After incubation, the DNA was extracted and examined for the presence of aromatic adducts using the nuclease P1 modification of the 32P-postlabelling technique. The maps of PEI-cellulose plates and autoradiography showed that 92% of the radioactivity contained in DB[a,h]A-DNA adduct spots is derived from the related 3,4-diol and that about 50% of the adducts may be formed following the conversion of this diol to the bay-region anti- and syn-3,4-diol 1,2-oxides.
Chemico-Biological Interactions | 1983
W. H. Swallow; K. Pal; David H. Phillips; P.L. Grover; Peter J. Sims
The metabolism of 3H-labelled 7,12-dimethylbenz[a]anthracene (DMBA) and of 7-hydroxymethyl-12-methylbenz[a]anthracene (7-OHM-12-MBA) into solvent- and water-soluble and protein-bound derivatives has been examined in rat liver and adrenal homogenates and in rat adrenocortical cells in culture. Although the overall extents of metabolism of the substrates by the two types of homogenate were similar, there was twice as much binding to protein in incubations with the 7-hydroxymethyl derivative. Rat adrenal cells in culture metabolized DMBA more extensively than 7-OHM-12-MBA and converted much more of the parent hydrocarbon into water-soluble derivatives. Both hydrocarbons were metabolized to yield dihydrodiols that were separated and identified by high performance liquid chromatography (HPLC). The 8,9-dihydrodiol was the major dihydrodiol formed from DMBA but, with 7-OHM-12-MBA as substrate, metabolism was diverted to the 10,11- and 3,4-positions in adrenal and hepatic preparations respectively. The viability of rat adrenocortical cells in culture, as measured by trypan blue exclusion, did not appear to be affected by treatment with DMBA, 7-OHM-12-MBA, the sulphate ester of 7-OHM-12-MBA or by 3,4-dihydro-3,4-dihydroxy-7-hydroxymethyl-12-methylbenz[a]anthracene.
Chemico-Biological Interactions | 1990
M.S. Masento; G.W. Taylor; D. Watson; Albrecht Seidel; W. Bochnitschek; Franz Oesch; P.L. Grover
3-Hydroxychrysene, a metabolite of the polycyclic aromatic hydrocarbon (PAH) chrysene, was metabolised by rat liver microsomal preparations obtained from Arochlor 1254-pretreated rats. Eight major metabolites were isolated by high performance liquid chromatography and characterised by u.v. spectroscopy and a variety of mass spectrometric techniques. The metabolites were unambiguously identified as 9-hydroxy-trans-1,2-dihydroxy-1,2-dihydrochrysene and 9-hydroxy-r-1,t-2,t-3,c-4-tetrahydroxy-1,2,3,4-tetrahydrochrysene and tentatively identified as 3-hydroxy-trans-5,6-dihydroxy-5,6-dihydrochrysene (since chrysene is a symmetrical molecule the 3- and 9-positions are equivalent), 9-hydroxy-trans-3,4-dihydroxy-3,4-dihydrochrysene, 1,2,3-trihydroxy-1,2,3,4-tetrahydrochrysene, an oxidised phenol and two diphenols. These results indicate that 3-hydroxychrysene can be further metabolised via a number of different pathways including those involving the formation of phenol- and triol-epoxides.
Carcinogenesis | 2000
J. A. Williams; Finbarr C. Martin; Gordon Muir; A Hewer; P.L. Grover; David H. Phillips
International Journal of Cancer | 1979
David H. Phillips; P.L. Grover; Peter J. Sims