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Biomedical subjects

T J Slaga

Publications and source records attributed to T J Slaga.

At least 271 records · Page 15Linked to original sources
PubMed1976

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↗
PubMed1976

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↗
PubMed1976

Mouse epidermal aryl hydrocarbon hydroxylase.

Mouse skin contains a NADPH-dependent, aryl hydrocarbon hydroxylase (AHH), which is inducible by polycyclic aromatic hydrocarbons. In general, unsubstituted polycyclic hydrocarbons caused a greater induction of epidermal AHH than substituted one (1,2,3,4-dibenzanthracene greater than 1,2,5,6-dibenzanthracene greater than benz (a)anthracene equal 3-methylcholanthrene greater than 7,12-dimethlbenz (a)anthracene) which did not correlate with their ability to initiate tumors in mouse skin. Two different techniques were used to isolate epidermis and similar results were obtained with both. However, the technique of isolating epidermis using a mild heat treatment required that the temperature be maintained at 52 degrees C for 30 sec. If the temperature was raised to 54 degrees C or above, there was a large reduction in the AHH activity. Isolated epidermis has 4 to 5 times the AHH activity as dermis and about twice that of whole skin. This was true for control mice or mice in which AHH was induced by pretreatment with benz(a)anthracene.

Animals↗
PubMed1976

The influence of prolonged ACTH treatment on rat adrenal steroidogenesis.

A series of in vitro experiments using pregnenolone-14C-4 and progesterone-14C-4 as precursors were performed to determine the effects of prolonged ACTH administration on adrenal steroid biogenesis in the rat. Under ACTH administration there was a tendency for the isolated steroids to have larger quantities and specific activities from both precursors than under control conditions. In contrast to the rabbit, the rat did not produce any detectable amounts of 17 alpha-hydroxylated steroids under either control or prolonged ACTH treatment using the very sensitive double isotope derivative assay for quantitation.

Adrenal Glands↗
PubMed1975

Acetic acid, a potent stimulator of mouse epidermal macromolecular synthesis and hyperplasia but with weak tumor-promoting ability.

The effects of a single application of various dose levels of acetic acid or the weak tumor promoter, phorbol-12,13-ditetradecanoate, on the incorporation of tritiated thymidine (3H-TDR), 3H-cytidine, and 3H-leucine into DNA, RNA, and protein of mouse epidermis, respectively, were determined and compared with histologic changes in the skin. Treatment with either 500 or 833 mumoles acetic acid induced a sequential and sustained stimulation of RNA, protein, and DNA synthesis, which was followed by extensive epidermal hyperplasia similar to that reported for the strong promoter and irritant, 12-O-tetradecanoyl-phorbol-13-acetate. A dose-response relationship between the amount of acetic acid and the rate of DNA synthesis was found between the dose levels of 33 to 833 mumoles of acetic acid per application. The latter dose induced the maximum activation of 3H-TDR into DNA at 723% of control at 2 days, whereas 33 mumoles stimulated DNA synthesis earlier and peaked at 210% of control at 3 hours. Phorbol-12,13-ditetradecanoate also stimulated macromolecular synthesis in a similar sequence, though to a lesser degree. No observable inflammation and only a slight hyperplastic response were noted with phorbol-12,13-ditetradecanoate. Weekly applications of 667 mumoles of acetic acid produced a maximal tumor response of 0.73 papilloma/mouse after 32 weeks of promotion. However, a weekly dose of 677 mumoles of acetic acid was essentially inactive when given in two divided doses. When croton oil was administered twice weekly at a 0.25%-dose level, 10.2 papillomas/mouse were induced after 32 weeks of promotion. The results showed that the previously considered nonpromoting inflammatory agent, acetic acid, must be a weak promoter. However, there was no correlation between stimulated macromolecular synthesis or hyperplasia and tumor promotion when phorbol esters were compared with acetic acid.

Acetates↗
PubMed1975

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↗
PubMed1975

Prolonged inhibition of mouse epidermal DNA synthesis by dexamethasone.

The effect of dexamethasone, an anti-inflammatory agent that inhibits skin carcinogenesis, on DNA, RNA, and protein synthesis in mouse epidermis was investigated. Within 1 hour after the topical application of 75 mug dexamethasone to the skin of mice, epidermal DNA synthesis was inhibited drastically and lasted for approximately 5 days, followed by a biphasic stimulation at 7 and 10 days after treatment. Histologically, the skin after dexamethasone treatment revealed only subtle quantitative changes. The dermis was not altered. The epidermal thickness was unchanged, but the nuclei of the epidermal cells were more densely stained and the chromatin was more densely clumped. These changes were present by 12 hours and persisted for 10 days. Both epidermal RNA and protein syntheses were stimulated early, reached a peak of around 180% of controls at 1 hour, but returned to control levels by 3 hours. They were slightly inhibited between 3 and 12 hours after treatment and then returned to control levels. This prolonged inhibition of DNA synthesis by dexamethasone may be related to its anticarcinogenic effect.

Administration, Topical↗