Effects of dietary intake of a fungal beta-D-glucan derivative on the level of DNA damage induced in primary rat hepatocytes by various carcinogens.
Water-soluble derivative of chitin-glucan complex used in our study, carboxymethyl chitin-glucan (CM-CG), enables oral administration without harmful side-effects, which can occur upon parenteral administration of the insoluble fungal beta-D-glucans. The aim of this study was to determine in ex vivo experiments the effects of dietary CM-CG on the level of DNA lesions in primary rat hepatocytes induced by various indirectly acting carcinogens. Multiorgan carcinogen benzo[a]pyrene (BaP); two hepatocarcinogens, dimethyldibenzocarbazole (diMeDBC) and N-nitrosomorpholine (NMOR); as well as a complex mixture of organic compounds adsorbed on ambient air particles (TP-S) were used for this purpose. The amount of DNA lesions was assessed using the comet assay and the micronucleus test. In addition, the mitotic indexes and the frequencies of necrotic and apoptotic cells were evaluated as well. Our results showed that the diet enriched with CM-CG (200 mg/kg of body weight) during 21 days did not induce any negative effect on DNA nor did the mitotic indexes and the frequencies of necrotic and apoptotic cells differ statistically from the controls. On the other hand, the hepatocytes isolated from CM-CG fed animals were more resistant to the action of all genotoxins used in our study [BaP (5-20 microM), diMeDBC (0.2-2 microM), NMOR (3.4-10.2 mM), TP-S (5-20 microM)]. We can conclude that in addition to the known immunopotentiating activity of beta-D-glucans, they can efficiently inhibit the genotoxicity of carcinogens requiring metabolic activation in rat heptocytes.
Lazarová
Monika
M
Cancer Research Institute SAS, Vlárska 7, 83391 Bratislava, Slovakia. monika.lazarova@savba.sk
Lábaj
Juraj
J
Eckl
Peter
P
Kogan
Grigorij
G
Slamenová
Darina
D
D000818:Animals; D016587:Antimutagenic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity; D002478:Cells, Cultured; D002686:Chitin / Q000008:administration & dosage / Q000031:analogs & derivatives; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005936:Glucans / Q000008:administration & dosage; D022781:Hepatocytes / Q000187:drug effects*; D008297:Male; D015162:Micronucleus Tests; D008938:Mitosis / Q000187:drug effects*; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D047071:beta-Glucans / Q000008:administration & dosage*
D016587:Antimutagenic Agents; D002273:Carcinogens; D005936:Glucans; D047071:beta-Glucans; C091649:carboxymethyl-chitin-glucan; D002686:Chitin