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K Pal

Publications and source records attributed to K Pal.

49 records · Page 3Linked to original sources

The involvement of a non-'bay-region' diol-epoxide in the metabolic activation of benza[a]anthracene in hamster embryo cells.

The major hydrocarbon-nucleoside adduct present in hydrolysates of DNA from hamster embryo cells that had been treated with 3H-labelled benz[a]anthracene in culture has been examined by chromatography on Sephadex LH-20 columns and by high-pressure liquid chromatography. The results show that this adduct most probably arises from r-8,t-9-hydroxy-t-10,11-oxy-8,9,10,11-tetrahydrobenz[a]anthracene (anti-BA-8,9.-diol 10,11-oxide). On the basis of this and other evidence, this non-bay-region diol-epoxide appears to be a reactive intermediate involved in the metabolic activation of benz[a]anthracene.

Animals↗

The metabolism of benzo(a)pyrene by Chinese hamster ovary cells in culture.

1. The metabolism off the carcinogenic polycyclic hydrocarbon, benzo(a)pyrene, in Chinese hamster ovary cells in culture has been investigated. 2. Products with the properties on h.p.l.c. of 3-hydroxybenzo(a)pyrene and the trans-4,5-, 7,8- and 9,10-dihydrodiols of benzo(a)pyrene were detected in the cell medium when cells were incubated with benzo(a)pyrene for 24 h. 3. Examination of the nucleoside adducts present in hydrolysates of the DNA of Chinese hamster ovary cells that had been incubated with benzo(a)pyrene showed the presence of a product that co-chromatographed on Sephadex LH20 columns with the nucleoside adduct obtained from DNA that was allowed to react with the anti-isomer of the 7,8-dihydrodiol 9,10-epoxide of benzo(a)pyrene.

Animals↗

The induction of sister chromatid exchanges by dihydrodiols derived from 7,12-dimethylbenz[a]anthracene and 3-methylcholanthrene.

The in vitro induction of sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells by the polycyclic hydrocarbons, 7,12-dimethylbena[a]anthracene and 3-methylcholanthrene and some of the related dihydrodiols was investigated. Increased numbers of SCEs were seen in the chromosomes of cells exposed to non-K-region dihydrodiols. The most active compounds were the 3,4-dihydrodiol of 7,12-dimethylbenza[a]anthracene and the 7,8- and 9,10-dihydrodiols of 3-methylcholanthrene: the parent hydrocarbons and their corresponding K-region dihydrodiols were relatively less active. The results are consistent with others that suggest that the metabolic activation of both hydrocarbons proceeds through the conversion of non-K-region dihydrodiols into vicinal diol-epoxides.

9,10-Dimethyl-1,2-benzanthracene↗

Induction of sister-chromatid exchanges in Chinese hamster ovary cells treated in vitro with non-K-region dihydrodiols of 7-methylbenz[a]anthracene and benzo[a]pyrene.

Studies were carried out on the incidence of sister-chromatid exchanges induced in Chinese hamster ovary cells by in vitro treatment with the polycyclic aromatic hydrocarbons 7-methylbenz[a]anthracene and benzo[a]pyrene and with related K-region and non-K-region dihydrodiols. Appreciable increased in the incidence of sister-chromatid exchanges were apparent in cells treated with non-K-region dihydrodiols: the most active compounds were 3,4-dihydro-3,4-dihydroxy-7-methylbenz[a]anthracene and 7,8-dihydro-7,8-dihydroxybenzo[a]pyrene and the effects were dose-dependent. The parent hydrocarbons and the related K-region dihydrodiols induced some sister-chromatid exchanges but they were considerably less active than these two non-K-region diols. The results suggest that this system may usefully be applied to studies aimed at determining which dihydrodiols are important in the metabolic activation of the carcinogenic polycyclic hydrocarbons. These and other results also infer that Chinese hamster ovary cells possess some intrinsic ability to metabolize such compounds in the absence of exogenous activation systems.

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The involvement of a diol-epoxide in the metabolic activation of benzo(a)pyrene in human bronchial mucosa and in mouse skin.

DNA has been isolated from human bronchial segments that have been treated in short-term organ culture with 3H-labelled benzo (a) pyrene. DNA has also been isolated from mouse skin treated with 3H-labelled samples of benzo (a) pyrene, with the related radioactive 4,5-, 7,8- and 9,10-dihydrodiols and with 3H-3-hydroxybenzo (a) pyrene. Sephadex LH20 column chromatography of hydrolysates of these DNA samples showed that the hydrocarbondeoxyribonucleoside products formed in benzo (a)-pyrene-treated human bronchial mucosa and mouse skin are indistinguishable from those that are formed when 7,8-dihydro-7,8-dihydroxybenzo (a) pyrene 9,10-oxide reacts with DNA in solution. These same hydrocarbon-deoxyribonucleoside products were also found in hydrolysates of DNA from mouse skin treated with 7,8-dihydro-7,8-dihydroxybenzo (a)-pyrene but products of this type were not detected in hydrolysates of DNA following treatment of mouse skin either with the 4,5- or 9,10-dihydrodiols or with 3-hydroxybenzo (a) pyrene. This results show that the metabolic activation of benzo (a) pyrene to a diolepoxide, 7,8-dihydro-7,8-dihydroxybenzo (a) pyrene 9,10-oxide, which reacts with DNA, is the same in human bronchial mucosa, a tissue in which this hydrocarbon is suspected of being carcinogenic, as it is in mouse skin and in hamster embryo cells, two situations in which benzo(a)pyrene is known to induce malignancy.

Animals↗