|
| |
|
| |
|
|
Metabolism of and DNA Adduct Formation by Carcinogenic o-Anisidine and its Metabolite N-(2-Methoxyphenyl) hydroxylamine
Naiman, Karel ; Stiborová, Marie (advisor) ; Sofrová, Danuše (referee) ; Befekadu, Asfaw (referee)
CHARLES UNIVERSITY IN PRAGUE FACULTY OF SCIENCE DEPARTMENT OF BIOCHEMISTRY Metabolism of and DNA Adduct Formation by Carcinogenic o-Anisidine and its Metabolite N-(2-Methoxyphenyl)hydroxylamine Summary of Ph.D. Thesis RNDr. Karel Naiman Supervisor: Prof. RNDr. Marie Stiborová, DrSc. PRAGUE 2010 Introduction - 2 - INTRODUCTION Aromatic amines are potent toxic or carcinogenic compounds, presenting a considerable danger to the human population (NTP, 1978; IARC, 1982; Garner et al., 1984). They are widely distributed environmental pollutants found in workplaces (e.g. in chemical industry), in emissions from diesel and gasoline engines and on the surface of ambient air particulate matter (NTP, 1978; IARC, 1982), where they add to local and regional pollution (car exhausts, technological spills). Their toxicity and carcinogenicity has been widely examined, but the knowledge in metabolism of several aromatic amines and their physiological effects in humans are still incomplete. This is also the case of o-anisidine. 2-Methoxyaniline (o-anisidine, Fig. 1) is a potent carcinogen, causing tumours of the urinary bladder in both genders of F344 rats and B6C3F1 mice (NTP, 1978; IARC, 1982). The International Agency for Research on Cancer (IARC) has classified o-anisidine as a group 2B carcinogen (IARC, 1982), which is...
|
|
|
Ghrelin analogs in food intake regulation
Pýchová, Miroslava ; Ryšlavá, Helena (advisor) ; Sofrová, Danuše (referee)
Ghrelin analogs in food intake regulation Ghrelin, to date the only known peripherally produced and centrally acting peptide that stimulates food intake, is mainly synthesized in the stomach and acts through growth- hormone-secretagogue receptor (GHS-R). In addition to its orexigenic effect, ghrelin stimulates growth hormone (GH) release, gastric motility and acid secretion. The diverse functions of ghrelin raise the possibility of its clinical application for GH deficiency, eating disorders, and gastrointestinal diseases. Ghrelin agonists could be a promising therapeutics in cachexia occurring at cancer or chronic inflammatory diseases. Octanoylation of Ser3 is crucial for preservation of ghrelin activity. In this study, biological properties (binding to GHS-R, food intake stimulation in mice) of full length and shorter ghrelin analogues with octanoic acid coupled to diaminopropionic acid (Dpr) replacing Ser3 or without octanoic acid were followed. This substitution resulted in a prolonged stability and orexigenic effect of above mentioned ghrelin analogues. Importance of N-terminal part of ghrelin and octanoylation peptide was also confirmed.
|
|
| |
|
| |
guest ::
