OCENA ZNACZENIA FLAWONOIDÓW JAKO CZYNNIKA CHEMOPREWENCJI PRZED TOKSYCZNYM I RAKOTWÓRCZYM DZIA£ANIEM KSENOBIOTYKÓW O GENETYCZNIE UWARUNKOWANYM METABOLIZMIE.

Many toxic or carcinogenic substances reveal their harmful properties only when activated to a compound with high affinity to nucleophylic groups, which are present in proteins and nucleic acids. After binding to DNA these compounds may induce carcinogenic mutation of genetic material. Increased activation or reduced detoxication of potentially carcinogenic xenobiotics disturbs cellular equlibrium and leads to carcinogenesis. Flavonoids and furanocoumarines contained in grapefruit juice were known to inhibit activity of many enzymes and were shown to inhibit in vitro activity of isoenzyme CYP2D6 with genetically induced polymophism. The aim of this work was to assess the significance of grapefruit juice flavonoids and furanocoumarines as chemopreventive factors against toxic and carcinogenic activity of xenobiotics with genetically determined metabolism by determining their influence on cytochrome P450 isoenzyme CYP2D6 activity. Material and metod. The trial included 32 healthy volunteers taking in grapefruit juice (16), orange juice (8) or fresh water (8). Oxidative phenotype and genotype were determined by analytic methods. Phenotype tests conducted prior to and after commencement of 5 days long intake of correspondingly grapefruit juice, orange juice or water revealed differences in metabolic ratio (MR) values among groups. Results. Grapefruit juice drinkers had mean value of metabolic ratio (MR) increased by 34%. Conclusions. Our investigation have shown that regular grapefriut juice consumption may be cosidered only as supportive measure against toxic and carcinogenic influence of environmental factors and industrial polution such as combustion gases, cigarette smoke and other toxic substances, particularly in patients with high risk of cancer. [ABSTRACT FROM AUTHOR]