Hamsters

Safety. Magnesium oxide (fume) has a permissible exposure limit (PEL) (134) (8 hours, TWA), of 10 mg/m total dust and 5 mg/m respirable fraction. Tumorigenic data (intravenous in hamsters) show a TD q of 480 mg/kg after 30 weeks of intermittent dosing (135), and toxicity effects data show a TC q of 400 mg/m for inhalation in humans (136). Magnesium oxide is compatible with most chemicals exceptions are strong acids, bromine pentafluoride, chlorine trifluoride, interhalogens, strong oxidizers, and phosphorous pentachloride. 

Chronic Toxicity. The effects of repeated oral exposure to phthalates for periods ranging from a few days to 2 years have been studied in a number of animal species including rats, mice, hamsters, guinea pigs, ferrets, and dogs (37). 

Teratogenic effects have been noted with 2- and 4-aminophenol in the hamster, but 3-aminophenol was without effect in the hamster and rat (129,130). 4-Aminophenol is known to inhibit DNA synthesis and alter DNA stmcture in human lymphoblasts (131,132) and is mutagenic in mouse micronuclei tests (133). The aminophenols have been shown to be genotoxic, as evidenced by the induction of sister chromatid exchanges (134,135), but they also exert a protective effect against DNA interaction with other noxious chemicals (136). After assessment of available data a recent report stated that the aminophenols were safe as cosmetic ingredients in their present uses and concentrations (137). 

Leukotrienes. Leukotrienes, products of the Hpoxygenase pathway, are generally less radioprotective than the PGs, with the exception of LTC4, which is among the most potent of the naturally occurring eicosanoids (214). LTC radioprotects V79 hamster cells in vitro and mouse CEU-S and... 

Vaccine candidates are based on the two viral surface proteins, gD and gB (80). Recombinant methods are used to express the proteins, either in Chinese hamster ovary (CHO) cells or in baculovims. The proteins are purified as subunits and formulated with different adjuvants. Clinical trials with these vaccine candidates have been performed, but the results to date have not been encouraging. 

The recommended daily allowance for vitamin E ranges from 10 international units (1 lU = 1 mg all-rac-prevent vitamin E deficiency in humans. High levels enhance immune responses in both animals and humans. Requirements for animals vary from 3 USP units /kg diet for hamsters to 70 lU /kg diet for cats (13). The complete metaboHsm of vitamin E in animals or humans is not known. The primary excreted breakdown products of a-tocopherol in the body are gluconurides of tocopheronic acid (27) (Eig. 6). These are derived from the primary metaboUte a-tocopheryl quinone (9) (see Eig. 2) (44,45). 

Bredinin, Neosidomycin, and SF-2140. Bredinin (62), isolated from the culture filtrates of Eupenicillium brefeldianum (1,4), inhibits the multiplication of L5178Y, HeLa S3, RK-13, mouse L-ceUs, and Chinese hamster cells. GMP can reverse the inhibition by (62), but (62) is not incorporated into the nucleic acids. The inhibition of nucleic acid synthesis and chromosomal damage in the S and G 2 phases that is caused by (62), is reversed by GMP. It blocks the conversion of IMP to XMP and XMP to GMP. In combination with GMP, (62) interferes with intracellular cAMP levels and thereby inhibits cell division. 

Topical apphcation of ara-HxMP, C2QH23N40gP, significantly inhibited the development of keratitis-induced HSV-1, HSV-2, or vaccinia vims in the eyes of rabbits. Ara-HxMP also significantly controlled the development of HSV-1 or vaccinia viral-induced encephaUtis in mice and was also active in preventing equine abortion viral deaths in hamsters. Clinical trials with ara-HxMP have not yet been reported. 

Benzyl chloride also induced in vitro cellular transformation in Syrian hamster embryo cultures and DNA alkylation in several organs of the male mouse following iv adrninistration. In summary, lARC states there is limited evidence that benzyl chloride is carcinogenic in experimental animals epidemiological data was inadequate to evaluate carcinogenicity to humans (67). 

Reproductive Toxicity. No data are available that impHcate either hexavalent or trivalent chromium compounds as reproductive toxins, unless exposure is by way of injection. The observed teratogenic effects of sodium dichromate(VI), chromic acid, and chromium (HI) chloride, adininistered by injection, as measured by dose-response relationships are close to the amount that would be lethal to the embryo, a common trait of many compounds (111). Reported teratogenic studies on hamsters (117,118), the mouse (119—121), and rabbits (122) have shown increased incidence of cleft palate, no effect, and testicular degeneration, respectively. Although the exposures for these experiments were provided by injections, in the final study (122) oral, inhalation, and dermal routes were also tried, and no testicular degeneration was found by these paths. 

In the procedure for the surface test (313), the vims is grown in a monolayer of baby hamster kidney cells and incubated in Eagles medium supplemented with tryptose phosphate broth and calf semm. After separation of the vims from the cells by sonification and centrifugation, amounts of the suspension containing 3 x 10 plaque-forrning units are dried on coversHps. The inoculated coversHps are placed in 5 ml of the disinfectant for 1, 5, or 10 min, then rinsed, sonicated, and assayed. 

B. Cytogenetic analysis in cultured Chinese hamster or human cells... 

Marsh, J. P., and Mossman, B. L (1991) Role of asbestos and active oxygen species in. ictiva-rion. and expression of ornirhinc decarboxylase in hamster tracheal epithelial cells. Cancer Ra. 51(1), 167-173. 

Another application shows the preparative purification and polishing of a therapeutic fusion protein with a humanized recombinant IgG protein. The fusion protein was expressed by the fermentation of baby hamster kidney cells. The filtered culture supernatant (155 liters) contained 2.2 g of IgG and 75.5 g of total protein. After the immunoglobulins were isolated by expanded bed adsorption and rebuffering, the IgG fraction was bound to Fractogel EMD SOj (M). This column achieved baseline separation of complete antibodies (fusion protein) from small amounts of antibodies lacking the fusion part. The resulting highly purified IgG fraction (110 ml) was diluted to 150 ml and... 

L Na -iiidepeiideiit Braiiched-chaiii and aromatic amino acids Ehrlich ascites cells Chinese hamster ovary cells Hepatocytes... 

The different furanones 104 were tested for their potency as inhibitors of PGE2 production both in transfected Chinese hamster ovarian (CHO) cells expressing human COX-2 and in human whole blood. Compound 104r proved to be an orally active and selective COX-2 inhibitor that is devoid of the ulcerogenic effect at >100 times the dose for antiinflammatory, analgesic, and antipyretic effects (99BMC3187). 

FIGURE 2.11 Receptor-occupancy curves for activation of human calcitonin type 2 receptors by the agonist human calcitonin. Ordinates (response as a fraction of the maximal response to human calcitonin). Abscissae (fractional receptor occupancy by human calcitonin). Curves shown for receptors transfected into three cell types human embryonic kidney cells (HEK), Chinese hamster ovary cells (CHO), and Xenopus laevis melanophores. It can be seen that the different cell types lead to differing amplification factors for the conversion from agonist receptor occupancy to tissue response. 

Virus, adeno- 144, 154, 156 —, avian myeloblastosis 143 —, fowl plaque 144, 154 —, hamster melanoma 143... 

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