ABSTRACT
In this study, mutagenic and genotoxic potential of anti-tumor compounds avarol, avarone, and its derivatives 3'-methoxyavarone, 4'-(methylamino)avarone and 3'-(methylamino)avarone was evaluated and compared to cytostatics commonly used in chemotherapy (5-fluorouracil, etoposid, and cisplatin). Mutagenic potential of selected hydroquinone and quinones was assessed in prokaryotic model by the SOS/umuC assay in Salmonella typhimurium TA1535/pSK1002. Genotoxic potential was also assessed in eukaryotic models using comet assay in human fetal lung cell line (MRC-5), human adenocarcinoma epithelial cell line (A549), and in human peripheral blood cells (HPBC). The results indicated that avarol and avarone do not exert mutagenic/genotoxic potential. Among the studied avarone derivatives, mutagenic potential was detected by SOS/umuC test for 3'-(methylamino)avarone, but only after metabolic activation. The results of comet assay indicated that 3'-methoxyavarone and 3'-(methylamino)avarone have a significant impact on the level of DNA damage in the MRC-5 cell line. Genotoxic potential was not observed in A549 cells or HPBC probably due to a different uptake rate for the compounds and lower in metabolism rate within these cells.
Subject(s)
Cyclohexenes/toxicity , Sesquiterpenes/toxicity , A549 Cells , Cell Line, Tumor , Comet Assay , DNA Damage , Humans , Male , Mutagens/toxicity , Salmonella typhimurium/drug effects , Toxicity TestsABSTRACT
BACKGROUND: The number of adolescents who use caffeine is constantly increasing. As juvenile age is vulnerable, it is reasonable to expect that they will differently perceive reason and react to caffeine use than adults, and be more prone to unwanted physiological and psychological consequences of its consumption. AIM: Analysis of the scope and pattern of caffeine consumption among adolescents in Serbia. STUDY DESIGN: The cross-sectional survey was implemented in the study population of 191 Serbian adolescents during 2010. RESULTS: The median daily intake of caffeine was 95.6 mg. The major source of caffeine was brewed coffee, and the most common reasons for caffeine intake were leisure, peer influence, or habit. Only 57.6% of the subjects were aware that caffeine is present in consumed beverages. Sex affected the pattern, but not the overall level, of caffeine consumption. No association between caffeine consumption and smoking status, frequency of caffeine use in the family, or negative personal experience with caffeine effects was observed. CONCLUSION: Our investigation provides first and rather detailed insight into caffeine-containing beverage consumption scope and pattern among Serbian adolescents. For accurate estimation and analysis of caffeine intake in this population, randomized studies with prospective longitudinal design, caffeine content measurement, and more subjects involved are warranted.
ABSTRACT
PURPOSE: The purpose of this study is to investigate the effect of two of the most important functional CYP1A2 variations -3860G > A and -163C > A on carbamazepine pharmacokinetics in Serbian pediatric epileptic patients. METHODS: The study involved 40 Serbian pediatric epileptic patients on steady-state carbamazepine treatment. Genotyping for -3860G > A and -163C > A was carried out using PCR-RFLP method, and carbamazepine plasma concentrations were determined by high pressure liquid chromatography (HPLC) method. For pharmacokinetic analysis, NONMEM software with implementation of ADVAN 1 subroutine was used. RESULTS: CYP1A2 polymorphism -163C > A was found at the frequency of 65.0 %, while -3860G > A was not detected. The correlation between weight-adjusted carbamazepine dose and carbamazepine concentration after dose adjustment was significant only in carriers of -163C/C and C/A genotypes (r = 0.68, p = 0.0004). The equation that described population clearance (CL) was CL (l/h) = 0.176 + 0.0484 * SEX + 0.019 * CYP1A2 + 0.000156 * DD, where SEX has a value of 1 if male and 0 if female, CYP1A2 has a value of 1 if -163A/A and 0 if -163C/C or C/A, and DD is the total carbamazepine daily dose (mg/day). CONCLUSIONS: CYP1A2 -163A/A genotype influence carbamazepine pharmacokinetics. In addition to sex and total carbamazepine daily dose, -163C > A CYP1A2 polymorphism should be considered as a predictor of carbamazepine clearance.