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Biomedical subjects

P Sims

Publications and source records attributed to P Sims.

At least 127 records · Page 7Linked to original sources
PubMed1976

The conversion of benzo(alpha)pyrene 4,5-oxide into 4-hydroxybenzo(alpha)pyrene in the presence of polyriboguanylic acid.

Incubation of benzo[alpha] pyrene 4,5-oxide with poly(G) in neutral aqueous ethanol resulted in the formation of covalent adducts and in the production of free 4-hydroxybenzo[alpha]pyrene. This phenol, which was identified by its UV spectral properties and by its chromatographic characteristics, was also formed but at a much slower rate when the epoxide was incubated with DNA or with GMP. Phenol formation was not detected when benzo[alpha]-pyrene 4,5-oxide was incubated for prolonged periods in the presence of poly(A), poly(C) or poly(U) or in the absence of nucleic acid. Formation of 4-hydroxybenzo[alpha] pyrene from the epoxide in the presence of poly(G) was not accompanied by detectable base modifications or by breakage of phosphodiester linkages.

Benzopyrenes↗
PubMed1976

Tumour-initiating activities on mouse skin of dihydrodiols derived from benzo[a]pyrene.

Three dihydrodiols that are metabolites of benzo[a]pyrene and benzo[a]-pyrene itself have been tested in a comparative experiment for their activities as initiators of tumours in mouse skin. A single application (25 mug) of 4,5-dihydro-4,5-dihydroxybenzo[a]pyrene, of 7,8-dihydro-7,8-dihydroxybenzo[a]pyrene, of 9,10-dihydro-9,10-dihydroxybenzo[a]pyrene, or of benzo[a]pyrene was made to the shaved dorsal skin of adult female CDI mice; this was followed 2 weeks later by multiple thrice-or twice-weekly applications (1 mug) of 12-O-tetradecanoyl-phorbol-13-acetate as promoting agent. A control group of 30 mice received the promoting agent alone. The experiments were terminated 52 weeks after initiation. At this stage, all the groups contained mice bearing skin papillomas, some of which had progressed to malignancy. Quantitatively the results show that the 7,8-dihydrodiol is almost as active an initiator of mouse skin tumours as benzo[a]pyrene itself; the 4,5- and 9,10-dihydrodiols were significantly less active. The significance of these results is discussed in relation to the hypothesis that diol-epoxides are important in the metabolic activation of polycyclic hydrocarbons like benzo[a]pyrene.

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↗
PubMed1976

In vitro malignant transformation of mouse fibroblasts by non-K-region dihydrodiols derived from 7-methylbenz(a)anthracene, 7,12-dimethylbenz(a)anthracene, and benzo(a)pyrene.

The 8,9-dihydrodiols of 7-methylbenz(a)anthracene and 7,12-dimethylbenz(a)anthracene and the 7,8-dihydrodiol of benzo(a)pyrene, which are non-K-region diols with adjacent olefinic double bonds that can be metabolized to diol-epoxides, were more active than the parent hydrocarbons in inducing malignant transformation of M2 mouse fibroblasts; a fourth non-K-region diol, the 9,10-dihydrodiol of benzo(a)pyrene was less active than benzo(a)pyrene. The related K-region dihydrodiols, which lack adjacent olefinic double bonds, and 6-hydroxybenzo(a)pyrene were inactive, 7,8-Dihydrobenzo(a)pyrene, a more potent carcinogen than the 9,10 isomer, induced malignant transformation, but the 9,10 isomer was inactive. Transformed cells with abnormal morphology yielded sarcomas on injection into isologous mice; treated but morphologically normal cells did not. These results support the role of diols and diol-epoxides in the metabolic activation of polycyclic hydrocarbons.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1975

The carcinogenicity of polycyclic hydrocarbon epoxides in newborn mice.

Benz(a)anthracene injected subcutaneously during the first 3 days of life caused a dose related increase in the incidence of liver and lung tumours in Swiss mice but over a similar dose range, the K region epoxide of benz(a)anthracene was less effective. Neonatally injected 7-methylbenz(a) was considerably more active than its K region epoxide in increasing the incidence of liver tumours in males. Both the parent compound and the epoxide slightly raised the incidence of lung tumours. Both chrysene and its K region epoxide increased liver tumour incidence but not lung tumour incidence. The K region epoxides of dibenz(a,h)-anthracene and 3-methylcholanthrene were without apparent effect on the incidence of liver, lung or other tumours despite indications from previously reported studies that the parent hydrocarbons are active at the same dose levels. The K region epoxide of phenanthrene had no effect on the incidence of any kind of neoplasm.

Animals↗
PubMed1975

The activities of some polycyclic hydrocarbons and their "K region" epoxides in an in vitro-in vivo carcinogenicity test system.

Benz(a)anthracene, 7,12-dimethylbenz(a)anthracene, dibenz(a)anthracene and benzo(a)pyrene and their related "K region" epoxides were tested for carcinogenic activities using a system in which mouse lung tissue was incubated in the presence of the test compound for 30 min and then implanted into isologous mice. Only 7,12-dimethylbenz(a)anthracene showed any marked carcinogenic activity under the conditions used, but all the compounds tested produced extensive proliferative outgrowths in the implanted tissues that may represent specific responses to the carcinogens.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1975

Enzymic reduction of aromatic hydrocarbon epoxides by the microsomal fraction of rat liver.

1. The oxidation of aromatic hydrocarbons to arene oxides and the reduction of these oxides to the parent hydrocarbons are both catalysed by enzymes in the microsomal fraction of rat liver. A suggested name for the enzyme concerned in the reduction of these epoxides is 'epoxide reductase'. 2. 'Epoxide reductase' is NADPH-dependent and is inhibited by oxygen. 3. Preliminary investigations suggest that the enzyme is specific for both 'K-region' and 'non-K-region' arene oxides.

Animals↗
PubMed1975

Glutathione conjugates as metabolites of benz[a]anthracene.

1. [3H]Benz[a]anthracene is converted into water-soluble metabolites by microsomal plus soluble fractions of rat-liver in the presence of NADPH and glutathione. Chromatography on Sephadex G25 gave four radioactive peaks; the first contained hydrocarbon or hydrocarbon derivatives bound to soluble protein while the other three peaks contained glutathione conjugates of hydrocarbon metabolites. 2. Conjugates formed when either of the benz[a]anthracene metabolites, 5,6-dihydro-5,6-dihydroxybenz[a]anthracene or 8,9-dihydro-8,9-dihydroxybenz[a]anthracene, were similarly incubated were probably S-(5,6,8,9-tetrahydro-5,6,9-trihydroxybenz[a]anthracen-8-yl)glutathione and S-(5,6,8,9-tetrahydro-6,8,9-trihydroxybena[a]anthracen-5-yl)glutathione respectively. The corresponding peak obtained in the metabolism of benz[a]anthracene probably contains a mixture of these two isomers. 3. The third peak contained the conjugate, S-(5,6-dihydro-l-hydroxybenz-[a]anthracen-k-yl)glutathione, also formed by the conjugation of the "K-region" epoxide of benz[a]anthracene with glutathione. This was not formed in the metabolism of the dihydrodiols. 4. The fourth peak contained a new type of conjugate that is probably S-(8,9,10,11-tetrahydro-8,9,10-trihydroxybenz[a]anthracen-11-yl)glutathione. This conjugate is chromatographically similar to a product obtained from incubation of the 8,9-dihydrodiol, and is probably formed by microsomal oxidation of the 10,11-bond of the dihydrodiol, followed by conjugation of the resulting diol-epoxide with glutathione.

Animals↗