Showing papers by "Fred Hutchinson Cancer Research Center published in 1975"

Mouse mammary tumors: alteration of incidence as apparent function of stress.

Abstract: Eighty to 100 percent of female mice of the C3H/He strain carrying the Bittner oncogenic virus usually develop mammary tumors within 8 to 18 months after birth when studied under the usual housing and experimental conditions. By subjecting various groups of such mice to environmental circumstances providing different degrees of chronic stress, mammary tumor incidence at 400 days was modified, with incidences ranging from 92 percent under stress to 7 percent in a protected environment. The data suggest that moderate chronic or intermittent stress may predispose such mice to an increased risk of mammary carcinoma, possibly through a resultant compromise of their immunological competence or tumor surveillance system, and that adequate protection from physiological stress may reduce mammary tumor occurrence in mice.

Discrimination among some parametric models

Abstract: SUMMARY Linear models, with errors that follow the distribution of the logarithm of an F statistic, are shown to include a number of common statistical models as special cases. The error model is transformed and reparameterized to induce regular estimation on the boundary with one or both degrees of freedom infinite. This leads to bivariate score tests for normal, extreme value and logistic special cases as well as an evaluation of these models within a more general framework. In particular, the test for normality is found to reduce to the usual tests based on sample skewness and kurtosis. Sample sizes are given for pairwise discrimination among some specific models. Applications are indicated.

Acetic Acid, a Potent Stimulator of Mouse Epidermal Macromolecular Synthesis and Hyperplasia but With Weak Tumor-Promoting Ability

Abstract: 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.

Prolonged Inhibition of Mouse Epidermal DNA Synthesis by Dexamethasone

Abstract: 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.

Destruction of triplet nitrenium ion by ascorbic acid

Abstract: Die Reaktion des Karzinogens N-acetoxy-2-acetamidofluoren mit Guanosin wird durch Ascorbinsaure, jedoch nicht durch Zitronensaure gehemmt. Diese Hemmung bewirkt eine vermehrte Bildung von 2-Acetamidofluoren. Anscheinend reagiert Ascorbinsaure mit dem N-2-Fluorenyl-N-acetylnitreniumtriplett unter Bildung von Acetamidofluoren und oxidierter Ascorbinsaure.

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

Abstract: 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.

Mixed leukocyte culture reactivity in operationally tolerant rats: Relationship of lymphocyte-mediated reactivity and serum-blocking activity.

Abstract: Tolerance to Brown Norway (BN) allografts was induced in Wistar Furth (W/Fu) rats by neonatal inoculation of BN bone marrow cells or mixtures of (W/Fu × BN)F1 hybrid spleen and bone marrow cells. Lymphoid cells from rats in which operational tolerance had been induced (maintenance of BN skin graft for more than 100 days) were studied for mixed leukocyte culture (MLC) reactivity. Peripheral blood lymphocytes from 10 of 25 W/Fu rats operationally tolerant to BN skin grafts showed MLC reactivity when exposed to BN antigens in vitro, implying that some degree of MLC reactivity is compatible with prolonged skin graft survival. These same rats also showed cytotoxic activity to BN fibroblasts in vitro regardless of their MLC status. MLC is quantitatively decreased and possibly qualitatively altered as compared to that of control W/Fu lymphocytes. The decrease was specific for the tolerated antigens. Serum from the tolerant rats inhibited cytotoxic but not normal MLC reactivity of W/Fu cells against BN antigens.