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T J Slaga

Publications and source records attributed to T J Slaga.

At least 235 records · Page 13Linked to original sources
PubMed1979

Comparison of the skin tumor initiating activity of 3-methylcholanthrene and 3,11-dimethylcholanthrene in mice.

The abilities of 3-methylcholanthrene (3-MC) and 3,11-dimethylcholanthrene (3,11-DMC) to initiate skin tumors in Sencar mice were determined by using a 2-stage system of tumorigenesis. 3,11-DMC was found to have very weak skin tumor initiating activity when compared to the potent activity of 3-MC. The only difference between 3-MC and 3,11-DMC is the substitution of a methyl group in position 11 which is part of the 'K-region' or the 'peri' position. From these results, we suggest that an unhindered peri position adjacent to an angular benzene ring is necessary for carcinogenic activity of 3-MC.

Animals↗
PubMed1979

Potent tumor-initiating activity of the 3,4-dihydrodiol of 7,12-dimethylbenz(a)anthracene in mouse skin.

The abilities of the racemic trans-3,4-, 5,6-, and 8,9-dihydrodiols of 7,12-dimethylbenz(a)anthracene to initiate skin tumors in mice were determined by using a two-stage system of tumorigenesis. The 7,12-dimethylbenz(a)anthracene trans-3,4-dihydrodiol was found to be much more active as a tumor initiator than the parent hydrocarbon. The 7,12-dimethylbenz(a)anthracene trans-5,6- and 8,9-dihydrodiols were essentially inactive as skin tumor initiators. Our results suggest that the 3,4-dihydrodiol of 7,12-dimethylbenz(a)anthracene is a proximal carcinogen and that the "bay region" diol-epoxide may be the ultimate carcinogenic form of DMBA.

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

Inhibition of phorbol ester-induced tumor promotion in mice by vitamin A analog and anti-inflammatory steroid.

The effects of a vitamin A analog, TMMP ethyl retinoate [or ethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-trans-2,4,6,8-nonatetraenoate] (abbreviated Ro 10-9359), and an anti-inflammatory steroid, fluocinolone acetonide (or 6 alpha, 9 alpha-difluoro-11 beta, 16 alpha, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal) (abbreviated FA), given alone or together were studied in a two-stage carcinogensis system. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was used as the tumor promoter in a 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin system. Two stocks of female mice, CD-1 and Sencar, which differ in their degrees of sensitivity to skin carcinogenesis, were used. A dose-dependent inhibition of carcinogenic expression, as determined by a decreased number of papillomas per animal, was observed in each mouse stock with the use of both FA and Ro 10-9359 when given alone. When FA and Ro 10-9359 were given together, an enhanced effect on the lowering of tumor incidence was noted. FA effectively inhibited tumor formation in the sensitive mouse stock even when the steroid was given 1 day prior to TPA treatment under conditions of unusually high doses of initiator (DMBA) and/or promoter (TPA). These results suggest that both anti-inflammatory steroids and retinoids inhibit tumor promotion and can be effectively used as a combination regimen for increased chemopreventive response.

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

Effects of 12-O-tetradecanoylphorbol-13-acetate and mezerein on epidermal ornithine decarboxylase activity, isoproterenol-stimulated levels of cyclic adenosine 3':5'-monophosphate, and induction of mouse skin tumors in vivo.

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate and the antileukemic agent mezerein are diterpene esters of plant origin with certain structural similarities. Both compounds, when applied topically to mouse skin, were equipotent on a molar basis in inducing hyperplasia, inflammation, and ornithine decarboxylase activity, as well as in reducing cyclic adenosine 3':5'-monophosphate accumulation in response to beta-adrenergic stimulation. In contrast, mezerein was much less effective as a tumor promoter; the phorbol ester at 8.5 nmol/application yielded 78-fold more tumors than did 8.5 nmol mezerein per application to similarly initiated SENCAR mice. The superiority of the phorbol ester was nearly as great in CD-1 mice.

Animals↗
PubMed1978

Lack of tumor-promoting ability of certain environmental chemicals in a two-stage mouse skin tumorigenesis assay.

The food antioxidants butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) were tested as tumor promoters on CD1 female mice initiated with 7, 12-dimethylbenz(a)anthracene (DMBA). At a dose of 1 mg twice weekly they did not promote skin tumors. Nor did they produce tumors when tested as a complete carcinogen without DMBA initiation. The polychlorinated biphenyl Aroclor 1254 (PCB) and the polybrominated biphenyl Firemaster-6 (PBB) were also tested for their ability to promote skin tumors; at a 100 microgram dose twice weekly they were inactive. The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at a dose of 0.1 microgram twice weekly did not promote skin tumors in DMBA-initiated mice. TCDD, PCB, and PBB did not promote spontaneous tumors. None of the compounds at the dosages tested significantly increased the intrafollicular epidermis, nor did they appear to be chronically toxic to the test animals. These results indicate that dosage may be an important factor in promotion, since several of the tested compounds are known to be promoters in pulmonary and hepatic systems.

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

Lack of involvement of 6-hydroxymethylation in benzo[a]pyrene skin tumor initiation in mice.

The skin tumor-initiating activities of benzo[a]pyrene (BP), 6-hydroxymethylbenzo[a]pyrene (6-OH-CH2-BP), and 6-methylbenzo[a]pyrene (6-CH3-BP), as well as the effects of 7,8-benzoflavone (7,8-BF), quercetin, and 1-benzylimidazole on their activity, were determined in outbred female CD-1 mice by use of a two stage system of tumorigenesis. The skin tumor-initiating activity of 6-OH-CH2-BP and 6-CH3-BP was 12.5 and 20%, respectively, of the activity of BP, 7,8-BF had little effect on the skin tumor-initiating activity of 6-OH-CH2-BP and 6-CH3-BP. However, a dose-dependent inhibition of BP tumorigenesis by 7,8-BF was noted. Quercetin and 1-benzylimidazole also inhibited BP skin tumor-initiating activity. These findings indicated that direct hydroxymethylation of BP is not an important pathway in the activation of BP in mouse skin tumor initiation.

Animals↗
PubMed1978

Dibenz[a,c]anthracene: a potent inhibitor of skin-tumor initiation by 7,12-dimethylbenz[a]anthracene.

The mechanism by which the weak tumor initiator dibenz[a,c]anthracene (DB[a,c]A) inhibits the skin-tumor-initiating activity of 7,12-dimethylbenz[a]anthracene (DMBA) was investigated. DB[a,c]A was found to be a potent inhibitor of DMBA initiation when given either 5 min, or 1, 12, or 36 hours before DMBA. Pretreatment of mice with unlabeled DB[a,c]A at either 1, 12, or 36 hours before killing increased the in vitro epidermally mediated covalent binding of [3H]DMBA to DNA more than pretreatment with unlabeled DMBA at comparable times. Only when the tumor experiments were mimicked did a decrease in DMBA covalent binding to DNA in vitro occur. The results suggests that some competition at the level of polycyclic hydrocarbon metabolism or at the genome level may exist between metabolites of the weak carcinogen and those of the strong carcinogen.

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

Skin tumor-initiating activities of the twelve isomeric phenols of benzo(a)pyrene.

The skin tumor-initiating activities of the 12 isomeric phenols of benzo(a)pyrene (BP) were determined in mice by use of a two-stage system of tumorigenesis. 11-Hydroxybenzo(a)pyrene was moderately active, whereas 2-hydroxybenzo(a)pyrene and BP were strong tumor initiators when applied topically to CD-1 mice and followed by twice-weekly applications of the promoter 12-O-tetradecanoylphorbol-13-acetate. 1-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, and 12-hydroxybenzo(a)pyrene had less than 5% of the tumor-initiating activity of BP when the data were expressed as papillomas per mouse. After 30 weeks of promotion, the number of papillomas per mouse was 8.4, 8.5, and 2.8, respectively, for the animals treated with BP, 2-hydroxybenzo(a)pyrene, and 11-hydroxybenzo(a)pyrene. A 5-week latency period before the appearance of the first tumor was observed after the application of either 2-hydroxybenzo(a)pyrene or BP, whereas a slightly longer latency period of 7 weeks was observed following application of 11-hydroxybenzo(a)pyrene. The time required for 50% of the animals to develop tumors was 13 weeks for animals treated with BP and 15 weeks for animals treated with 2- or 11-hydroxybenzo(a)pyrene.

Animals↗
PubMed1978

Carcinogenicity and mutagenicity of benz(a)anthracene diols and diol-epoxides.

Benz(a)anthracene (BA) and its five possible trans-dihydrodiols were evaluated for determination of their skin tumor-initiating activity and their mutagenic activity in Chinese hamster V79 cells. In addition, the skin tumor-initiating abilities of five diol-epoxides of BA were tested. Results showed (+/-)-trans-3,4-dihydroxy-3,4-dihydrobenz(a)anthracene (BA 3,4-dihydrodiol) to be approximately 10 times more mutagenic than was BA and about 20 times more mutagenic than were the other possible dihydrodiols in the V79 cells cocultivated with irradiated hamster embryo cells. As a skin tumor initiator, BA 3,4-dihydrodiol was approximately 5 times more active than BA, whereas the other BA dihydrodiols were all less active tumor initiators. (+/-)-trans-3alpha,4beta-Dihydroxy-1alpha,2alpha-epoxy-1,2,3,4-tetrahydrobenz(a)anthracene was found to be approximately 20% more active as a tumor initiator than was BA 3,4-dihydrodiol, whereas the other diol-epoxides of BA were less active than BA itself. The results suggest that the bay-region diol-epoxide of BA may be the ultimate carcinogen and mutagenic form of BA.

Animals↗
PubMed1978

Metabolic conversion of 12-O-tetradecanoylphorbol-13-acetate in adult and newborn mouse skin and mouse liver microsomes.

Tritiated 12-O-tetradecanoylphorbol-13-acetate (TPA) was applied to adult mouse skin; at specified time intervals the mice were killed, and the labeled phorbol was extracted and subjected to separation and quantitation by high-pressure liquid chromatography. After 24 hr, TPA comprised greater than 96% of the recovered label from the skin, and its apparent half-life was 17.8 hr. Pretreatment of adult skin with TPA for 4 weeks before treatment with labeled TPA resulted in an increase in the clearance rate of TPA from the skin. Skin from newborn mice was capable of converting TPA into monoesters and phorbol, but the clearance rate in the adult was about 12 times more rapid than it was in the newborn. Epidermal homogenates converted TPA into 12-O-tetradecanoylphorbol, phorbol-13-acetate, and phorbol. Hepatic homogenates were able to convert TPA to monoesters and phorbol at rates 14 to 15 times faster than were epidermal homogenates. Attempts to isolate any previously undescribed metabolites of TPA by use of liver homogenates were unsuccessful, and mixed-function oxidation did not contribute to the metabolism of TPA. From inhibitor studies it was judged that esterases were implicated in the conversion of TPA to monoesters and phorbol. The results support the hypothesis that the tumor-promoting activity of TPA is directly related to its concentration in a specific tissue and that conversion of TPA to an active metabolite probably does not occur.

Animals↗