Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chronic toxicity and carcinogenicity of levobunolol, a nonselective beta-adrenoceptor antagonist, was evaluated in Swiss mice and Wistar rats. The drug was administered in the diet to mice at 0, 12, 50, and 200 mg/kg/day for 80 weeks and to rats at 0, 0.5, 2, 5, 30, and 180 mg/kg/day for 2 years. In mice, uterine leiomyomas were present in 4 of 50 females at 200 mg/kg but not in any other group. The incidences of other tumor types, as well as pathologic findings, were comparable among groups. In rats, significant body weight gain suppression occurred at 5, 30, and 180 mg/kg. Brown discoloration of perianal fur and steel-gray discoloration of hairless skin were evident in high-dose rats. A generalized steel-gray discoloration of internal organs and tissues occurred in the 30 and 180 mg/kg groups. No other differences between treated and control groups were evident. The clinical relevance of the increased incidence of uterine leiomyoma in mice is questionable because it occurred only in one species at more than 200 times the projected therapeutic dose.
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PMID:Chronic toxicity and carcinogenicity studies with the beta-adrenoceptor antagonist levobunolol. 135 Jul 67

The potential mutagenicity and carcinogenicity of commercial PCBs has been investigated in both in vivo and in vitro systems and several conclusions can be drawn from these studies. (1) PCBs can covalently adduct DNA both in vivo and in vitro (using a source of metabolic activation); the more highly chlorinated biphenyls are poorly metabolized and these compounds tend to exhibit very low binding to DNA. Based on the structure-activity relationships for PCBs (Safe, 1984) it is unlikely that the more toxic compounds such as 3,3',4,4',5-penta- and 3,3',4,4',5,5'-hexachlorobiphenyl, would form covalent adducts with DNA. (2) PCB mixtures and individual compounds exhibit minimal mutagenic activity in most assay systems. (3) The more highly chlorinated PCB mixtures (i.e. greater than 50% Cl by weight) are hepatocarcinogens in rodents whereas data from a limited number of studies suggest that the lower chlorinated mixtures are not carcinogenic. (4) In some model systems, the higher chlorinated PCB mixtures act as promoters of preneoplastic lesions and hepatocellular carcinomas in rodents treated with a variety of initiators. (5) Aroclor 1254 acts as a promoter of skin papilloma formation in HRS/J hairless mice and structure-activity and genetic studies suggest that the Ah receptor is necessary but not sufficient for the activity of halogenated aryl hydrocarbons as promoters in hairless mice. (6) Individual PCB congeners and higher chlorinated commercial mixtures also exhibit anti-carcinogenic activity in the CD-1 mouse skin cancer model. (7) Results from occupational studies suggest that individuals exposed to PCBs may have an excess of cancer at some sites, however, the most comprehensive study (Brown, 1987) suggests that there are no significant increases in the overall cancer rate in workers exposed to PCBs. Follow-up and continuing epidemiological studies on the PCB-exposed workers are required to further clarify the potential carcinogenic effects of PCBs on humans. In several strains of rats and mice, there is a high incidence of hepatic preneoplastic lesions and carcinomas and these lesions can be induced by diverse promoting agents (Schulte-Hermann et al., 1983; Weinstein, 1984). Since PCBs are not mutagenic and do not readily form covalent adducts with cellular DNA, it is likely that the higher chlorinated biphenyls are not genotoxic and act as promoters of carcinogenesis in rodents. A comparable mechanism has been suggested for 2,3,7,8-TCDD (Shu et al., 1987; Weinstein, 1984). For PCBs, the role of the Ah receptor in mediating their activity as promoters has not been delineated.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Polychlorinated biphenyls (PCBs): mutagenicity and carcinogenicity. 249 77

The rat dominant hairless gene (Ht) of the WBN/Ila-Ht rat causes atrichosis in Ht/Ht and hypotrichosis in Ht/+. Furthermore the Ht/Ht shows signs of abnormal keratinization and almost all of the Ht/Ht die in an immature stage before weaning in the conventional environment. Ht/+ was affected by dermatitis caused by Staphylococcus aureus, suggesting that the gene Ht might involve defense mechanisms against infection. In this study, we performed the linkage analysis of the gene Ht by outcross with the Brown Norway rat in the SPF environment. Ninety-six backcross progeny of (BN x WBN/Ila-Ht/Ht) F1 x WBN/Ila-Ht/Ht were typed with microsatellite markers and the gene Ht was mapped on chromosome 10 between Asgr1 and Nos2 within the map distance of 6.2 cM.
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PMID:Locus of dominant hairless gene (Ht) causing abnormal hair and keratinization maps to rat chromosome 10. 1088 53

Brown sugar has been used traditionally for the treatment of skin trouble as a component of soaps or lotions. Symptoms of aging including wrinkles and pigmentation develop earlier in sun-exposed skin than unexposed skin, a phenomenon referred to as photoaging. Ultraviolet B (UVB) radiation is one of the most important environmental factors influencing photoaging. The aim of this study was to clarify whether the nonsugar fraction of brown sugar prevents chronic UVB-induced aging of the skin using melanin-possessing hairless mice. The nonsugar fraction (1% or 3% solution, 50 mul/mouse) was applied topically to the dorsal region every day for 19 weeks. Both solutions prevented an increase in skin thickness and reduction in skin elasticity caused by the UVB. The 3% solution also prevented wrinkles and melanin pigmentation as well as increases in the diameter and length of skin blood vessels. Increases in the expression of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in UVB-irradiated skin was inhibited by the nonsugar fraction. Prevention of UVB-induced aging of the skin by topical application of the nonsugar fraction of brown sugar may be due to inhibition of increases in MMP-2 and VEGF expression.
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PMID:Effects of the nonsugar fraction of brown sugar on chronic ultraviolet B irradiation-induced photoaging in melanin-possessing hairless mice. 1905 Sep 91