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Biomedical subjects

A Dipple

Publications and source records attributed to A Dipple.

At least 109 records · Page 6Linked to original sources
PubMed1979

Comparison of metabolism-mediated binding to DNA of 7-hydroxymethyl-12-methylbenz(a)anthracene and 7, 12-dimethylbenz(a)anthracene.

Comparison of the binding to DNA of 7-hydroxymethyl-12-methylbenza(a)anthracene and 7, 12-dimethylbenz(a)anthracene (DMBA) catalyzed by mouse embryo cells in culture or by rat liver microsomes indicates that the products formed are different for the two hydrocarbons. Thus, the hydroxy compound is not an intermediate in the binding of DMBA to DNA in these systems. Binding of the hydroxy compound to DNA in mouse embryo cells is less efficient than for DMBA and is inhibited by 1,1,1-trichloropropylene 2,3-oxide, an inhibitor of epoxide hydrase. This and the fluorescence spectra of the hydroxy compound-DNA adducts indicate that the hydroxy compound is activated for DNA binding through the formation of a diol-epoxide in the 1,2,3,4-ring. As previously found for DMBA, this is consistent with the activation of this compound through a bay-region diol-epoxide.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Biochemical basis for cytotoxicity of 7,12-dimethylbenz(a)anthracene in rat liver epithelial cells.

When the effects of 7,12-dimethylbenz(a)anthracene (DMBA) on normal and malignant rat liver epithelial cells were compared in a colony inhibition assay, this carcinogen showed a preferential cytotoxic action on the normal cells. In investigations of the biochemical basis of this selective toxicity, it was found that both cell lines were similarly effective in binding DMBA to DNA and that both cell lines had the capacity to metabolize this carcinogen. However, the hepatoma cells were more efficient than were the normal cells in generating very polar metabolites (not organic solvent extractable). These studies suggest that the basis of the resistance of the hepatoma cells to the toxicity induced by DMBA lies in their ability to detoxify biologically active metabolites. Several phenols were examined as possible toxic metabolites of DMBA, but these were not toxic at dose levels at which DMBA kills most of the normal cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Evidence for the involvement of a diol-epoxide in the binding of 7,12-dimethylbenz(a)anthracene to DNA in cells in culture.

1,1,1-Trichloropropene 2,3-oxide (TCPO), a known inhibitor of the enzyme epoxide hydrase, inhibits binding of the carcinogen, 7,12-dimethylbenz(a)anthracene (DMBA), to the DNA of secondary mouse embryo cell cultures under conditions which do not appreciably decrease the overall metabolism of this carcinogen. This suggests that the formation of a transdihydrodiol is a necessary step in the metabolic pathway leading to DNA binding and that binding probably occurs through the generation of a reactive diol-epoxide. In concert with this, the major DMBA-DNA product isolated by chromatography on Sephadex LH-20 eluted with a methanol-water gradient is resolved into two separate components in a methanol-sodium borate solution gradient suggesting that, as is known for benzo(a)pyrene, two stereoisomeric diol-epoxides are involved in the binding of DMBA to DNA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Excision of hydrocarbon-DNA adducts and consequent cell survival in normal and repair defective human cells.

Survival curves for normal human cells and xeroderma pigmentosum variant cells (XP4BE) after ultraviolet radiation were indistinguishable. In comparison, cells from xeroderma pigmentosum complementation group A (XP12BE) were very sensitive to ultraviolet radiation. Complementation group C (XP2BE) cells were almost as sensitive as group A cells. These survival phenomena parallel to known unscheduled DNA synthesis responses of these cells to ultraviolet radiation, which, compared with normal cells, are: XP4BE, 100%; XP2BE, 20%; XP12BE, 2%. The relative capacities of these cells to excise 7-bromomethylbenz[a]anthracene-DNA adducts and to survive treatment with the carcinogen were similar to the responses to ultraviolet irradiation, except that the XP2BE cell line both excised and survived this damage far better than anticipated from its response to ultraviolet irradiation. Moreover, whilst in the normal cells and variant cells the ratio of hydrocarbon-adenine adduct to hydrocarbon-guanine adduct remaining in DNA decreased notably with excision, this ratio did not change significantly with excision in the XP2BE cell line. The relationship between greater excision capacity and increased cell survival in the experiments with the chemical carcinogen indicates that the unexcised damage is responsible for the cell-killing action of this agent. The different relative repair and survival responses of these cell lines to ultraviolet irradiation on the one hand, and to 7-bromomethylbenz[a]anthracene chemical carcinogen treatment on the other, indicate that in at least one of these cell lines (XP2BE), and possibly in all the lines, different cellular mechanisms are involved in the repair of DNA damage resulting from ultraviolet irradiation and that resulting from the chemical carcinogen treatment.

Benz(a)Anthracenes↗
PubMed1977

Photosensitivity of DNA-bound 7,12-dimethylbenz(alpha)anthracene.

Structural information about the products formed when 7,12-dimethylbenz(alpha)anthracene (DMBA) is bound to DNA in mammalian cell cultures has been sought through studies of the photosensitivities of these products and of various model compounds. Under conditions of light exposure in which the DNA-DMBA products were highly photosensitive, 8,9,10,11-tetrahydro-DMBA and 5,6-dihydro-DMBA were stable, whereas 9,10-dimethyl-anthracene and DMBA itself were highly photosensitive. This indicates that in the binding reaction with DNA, DMBA retains either the aromatic benz(alpha)anthracene nucleus or is metabolically activated in the 1,2,3,4-ring.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1977

Excision of 7-bromomethylbenz[a]anthracene--DNA adducts in replicating mammalian cells.

The excision of 7-bromomethylbenz[a]anthracene--DNA adducts was studied in two cell lines (HeLa S-3 and Chinese hamster V-79379A). In both cell lines, carcinogen-modified adenine residues were excised more readily than the modified guanine residues and the percentage of the total products excised decreased after treatment with higher concentrations of carcinogen. At the highest concentrations used in the Chinese hamster cells, neither DNA synthesis nor excision was detected. The lowest concentration used for these cells permitted almost 100% survival and all the DNA was replicated in a 30-h interval even though 50% of the initial damage was still present. The two- to threefold lower sensitivity of the Chinese hamster cells (compared with the Hela cells) to the carcinogen is attributed to this capacity for replication of DNA on a damaged template since the two cell lines' capacities for excision of the chemical damage were found to be comparable.

Benz(a)Anthracenes↗
PubMed1975

Endonuclease II of Escherichia coli: DNA reacted with 7-bromomethyl-12-methylbenz[alpha]anthracene as a substrate.

An endonuclease II preparation from Escherichia coli makes single strand breaks in DNA which has been treated with the carcinogen 7-bromomethyl-12-methylbenz[alpha]anthracene. In addition, the enzyme preparation excises N6-(12-methylbenz[alpha]anthracenyl-7-methyl)adenine and N2-(12-methylbenz[alpha]anthracenyl-7-methyl)guanine residues from the DNA. These are relased as the modified purine bases, not as purine nucleoside derivatives. The rate of release of the adenine derivative is three to four times that of the guanine derivative.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1972

Carcinogenic activity of some benz(a)anthracene derivatives in newborn mice.

Equimolar doses of 7-methylbenz(a)anthracene and 3 of its derivatives were given to newborn male and female Swiss mice. All 4 substances tested increased the risk of tumour development compared with that seen in control mice given the vehicle, arachis oil, only.7-Methylbenz(a)anthracene itself was the most actively tumorigenic of the compounds studied, giving rise to subcutaneous sarcomata at the site of injection, and multiple lung tumours and liver tumours. 7-Bromomethyl-12-methylbenz(a)-anthracene was similarly active in the lung and liver but evoked fewer subcutaneous sarcomata. 7-Bromomethylbenz(a)anthracene was seemingly slightly less active than either 7-methylbenz(a)anthracene or 7-bromomethyl-12-methylbenz(a)anthracene. 4-Chloro-7-bromomethylbenz(a)anthracene exhibited only marginal activity in that it slightly increased the risk of liver tumour development in male mice.

Animals↗