Search PubMed⌕ Search

Biomedical subjects

P Brookes

Publications and source records attributed to P Brookes.

At least 73 records · Page 4Linked to original sources
PubMed1976

(+/-)-7alpha,8beta-dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo(a)-pyrene is an intermediate in the metabolism and binding to DNA of benzo(a)pyrene.

The addition of borate buffer to the aqueous methanol used to elute hydrocarbon-deoxyribonucleoside derivatives from an LH 20 Sephadex column resulted in the separation of the products of reaction with DNA of the stereoisomers, (+/-)7alpha,8beta-dihydroxy-9alpha,10alpha-epoxy- and (+/-)-7alpha,8beta-dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrenes, i.e., the syn- and anti-benzo(a)pyrene-diolepoxide, respecitvely. By this technique it was shown that the microsome-mediated binding to DNA of benzo(a)pyrene-7,8-dihydrodiol involved exclusively the anti-benzo(a)pyrene-diolepoxide. The benzo(a)pyrene binding to DNA that resulted on exposure of BHK21/C13 cells to this carcinogen was also shown to result predominantly by reaction of the anti-benzo(a)pyrene-diolepoxide. However, in this case other derivatives, including the syn-benzo(a)pyrene diolepoxide, might also be involved.

Animals↗
PubMed1976

Comparison of the products of the reaction of 7-methylbenz(a)anthracene 5,6-oxide and RNA, with those formed in 7-methylbenz(a)anthracene-treated cells.

RNA was isolated by a phenol extraction method from mouse embryo cells treated in culture with either [G-3H]-7-methylbenz(a)anthracene or [G-3H]-7-methylbenz(a)anthracene 5,6-oxide (the K-region epoxide). The RNA was degraded to ribonucleosides, mixed with ultraviolet-absorbing quantities of the epoxide ribonucleoside products isolated from RNA that had reacted with 7-methylbenz(a)anthracene 5,6-oxide in aqueous ethanol solution, and chromatographed on a column of Sephadex LH-20 eluted with a methanol:water gradient. The 7-methyl-benz(a)anthracene 5,6-oxide ribonucleoside products formed in cells were identical to those formed in aqueous solution, although the relative amounts of the products varied. The majority of these epoxide-ribonucleoside products were not identical to the products formed in cells treated with the parent hydrocarbon. These results suggest that the major reactive form of 7-methylbenz(a)anthracene that binds to RNA in mouse embryo cells is not the K-region epoxide of this hydrocarbon.

Benz(a)Anthracenes↗
PubMed1975

Retention of tritium during the binding of tritiated benz(a)pyrene to DNA.

Chemical conversion of generally tritiated benzo(a)pyrene to 6 and 1,6-substituted derivatives resulted in 30% and 48% loss of tritium respectively. Metabolism of [3H], [14C]-benzo(a)pyrene by rat liver microsomes yielded 3-hydroxybenzo(a)pyrene with 30% loss of tritium, a mixture of quinones with 50% loss of tritium and three dihydrodiol metabolites which had retained all the tritium of the parent hydrocarbon. DNA isolated from mouse embryo cells which had been exposed to [3H], [14C]-benzo(a)pyrene, and DNA with this hydrocarbon bound following in vitro rat liver microsomal incubation were degraded enzymically and the hydrocarbon-deoxyribonucleoside products isolated. The tritium contents of the products obtained from both DNA samples were very close to those of the original double labelled benzo(a)pyrene. These results are inconsistent with a phenol or quinone intermediate being responsible for the reaction with DNA, but fully consistent with a diol epoxide intermediate as proposed by Sims et al. (1974).

Animals↗
PubMed1975

The nature of the deoxyribonucleosides involved in the binding of carcinogenic hydrocarbons to the DNA of mouse embryo cells.

The DNA of mouse embryo cells was specifically labelled in the purine moieties with (G(3)H)-deoxyadenosine or in the cytosine moieties with (5-(3)H)-deoxycytidine. These cells were then treated with 7-methylbenz (a) anthracene (7MBA) or benzo (a)-pyrene (B(a)P) and the DNA isolated, degraded and fractionated by LH20 Sephadex column chromatography. When the purines of the DNA were tritium-labelled, radioactive hydroccarbondeoxyribonucleoside products were obtained. No such products were found with deoxycytidine pre-labelled DNA. Contrary to an earlier suggestion, these results indicate that it is the purine moieties of DNA which react with the metabolically activated hydrocarbon derivative in vivo.

Animals↗
PubMed1975

The benzo(alpha)pyrene deoxyribonucleoside products isolated from DNA after metabolism of benzo(alpha)pyrene by rat liver microsomes in the presence of DNA.

Rat liver microsomes (induced by 3-methylcholanthrene) were used to catalyze the binding of tritium-labeled benzo(alpha)pyrene to DNA. Enzymic degradation of this DNA to deoxyribonucleosides, followed by separation of the products by Sephadex LH20 column chromatography, revealed two major products. One of these was shown to be the same as that obtained from DNA with benzo(alpha)pyrene bound following treatment of mouse embryo cells in culture with the carcinogen. Neither product resembled those obtained from DNA that had been caused to react with benzo(alpha)pyrene 4,5-oxide (K-region eposide). The aryl hydrocarbon hydroxylase activity of the microsome preparations was determined and related to the extent of microsome-catalyzed hydrocarbon binding. Inhibitors of the enzyme epoxide hydrase increased this binding but caused the loss of one of the two major products. On the basis of the results obtained, a model is proposed of the mechanism of benzo(alpha)pyrene metabolism and DNA binding.

Aryl Hydrocarbon Hydroxylases↗
PubMed1975

Comparison of the cellular DNA-bound products of benzo(alpha)pyrene with the products formed by the reaction of benzo(alpha)pyrene-4,5-oxide with DNA.

DNA isolated from mouse embryo cell cultures that had been treated with [3H]benzo(alpha)pyrene was degraded with enzymes to deoxyribonucleosides, and the hydrocarbon-deoxyribonucleoside products were isolated by chromatography on a Sephadex LH20 column eluted with a water: methanol gradient. The hydrocarbon-deoxyribonucleoside products were not identical to those found in similar chromatograms of enzyme digests of DNA that had been reacted with benzo(alpha)pyrene-4,5-oxide in aqueous ethanol solution. This finding suggests that the metabolic activation of benzo(alpha)pyrene that results in this hydrocarbon becoming covalently bound to DNA in mouse embryo cells in culture may be more complex than simply formation of a K-region epoxide and reaction of that compound with the cellular DNA.

Animals↗
PubMed1974

'Community outreach'.

Explore the source record for details and available documents.

Community Health Services↗