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Biomedical subjects

J D Scribner

Publications and source records attributed to J D Scribner.

At least 37 records · Page 2Linked to original sources

Skin tumor initiating ability of benzo(a)pyrene 4,5- 7,5- and 7,8-diol-9,10-epoxides and 7,8-diol.

The skin tumor initiating abilities of both K-region and non-K-region epoxides of benzo(a)pyrene(BP) were determined in mice using a two-stage system of tumorigenesis. BP-4,5-epoxide and BP-7,8-dihydrodiol-9,10-epoxide (anti) were found to be weak tumor initiators whereas BP-7,8-epoxide had about a third of the activity as the parent hydrocarbon, BP. However, the 7,8-dihydrodiol of BP was found to be approximately as potent as BP suggesting that it may be a proximate carcinogen.

Animals↗

Epidermal cell proliferation and promoting ability of phorbol esters.

Dose-response relationships on the abilities of several phorbol ester tumor promoters to promote skin tumors after 7,12-dimethylbenz[a]anthracene initiation and to bring about edema, inflammation, and epidermal hyperplasia were determined in female Charles River CD-1 mice. The promoting ability of the potent synthetic promoter, phorbol-12,13-dioctanoate (PdiC8), was determined over a dose range of 0.1-10 mug/application. Administration of PdiC8 two times weekly at dosages of 4, 6, 8, and 10 mug gave little variation in tumor response. A dose-dependent tumor response occurred at doses of 1-4 mug PdiC8. Only 1 papilloma was observed when PdiC8 was given twice weekly at a dose of 0.1 or 0.5 mug. A similar dose-response relation was observed for the ability of PdiC8 to stimulate epidermal hyperplasia. Investigations of other phorbol esters revealed an excellent correlation between their promoting ability and their ability to induce epidermal hyperplasia; however, that was not the case for compounds outside the phorbol ester series (i.e., acetic acid, cantharidin, and ethylphenylpropiolate).

9,10-Dimethyl-1,2-benzanthracene↗

Adducts between the carcinogen 2-acetamidophenanthrene and adenine and guanine of DNA.

The sulfate and acetate esters of the carcinogen N-hydroxy-2-acetamidophenanthrene attack calf thymus DNA in vitro to yield adducts of 2-acetamidophenanthrene with guanine and adenine in the DNA. These adducts were found to be 8-(N-2-phenanthrylacetamido)deoxyguanosine and N6-1-(2-acetamidophenanthryl)deoxyadenosine, respectively. These reactions, and the already known reactions of esters of N-hydroxy-2-acetamidofluorene, together with Hückel molecular orbital calculations, suggest that the relative tendencies of a series of N-aryl-N-acetylnitrenium ions to react with adenine and guanine may be predicted.

Acetamides↗

Tumor initiation by N-acyloxy derivatives of piperidine and N-arylacetamides.

Four N-Acetoxy-N-arylacetamides previously found to be local sarcomagens in the rat have been found to be initiators of tumorigenesis in mouse skin. The order of activity was: N-acetoxy-2-acetamidophenanthrene greater than N-acetoxy-4-acetamino-stilbene similar to N-acetoxy-2-acetamido-fluorene greater than N-acetoxy-4-acetamidobiphenyl. Two substituted N-benzoyloxypiperidines previously shown to yield nitrenium ions on solvolysis in methanol also had initiating activity in mouse skin.

Acetamides↗