Effects of crude extracts of Agaricus blazei on DNA damage and on rat liver carcinogenesis induced by diethylnitrosamine

The effects of crude extracts of the mushroom Agaricus blazei Murrill (Agaricaceae) on both DNA damage and placental form glutathione S-transferase (GST-P)-positive liver foci induced by diethylnitrosamine (DEN) were investigated. Six groups of adult male Wistar rats were used. For two weeks, animals of groups 3 to 6 were treated with three aqueous solutions of A. blazei (mean dry weight of solids being 1.2, 5.6, 11.5 and 11.5 mg/ml, respectively). After this period, groups 2 to 5 were given a single ip injection 200 mg/kg DEN and groups 1 and 6 were treated with 0.9 NaCl. All animals were subjected to 70 partial hepatectomy at week five and sacrificed 4, 24 and 48 h or 8 weeks after DEN or 0.9 NaCl treatments (10th week after the beginning of the experiment). The alkaline comet assay and GST-P-positive liver foci development were used to evaluate the influence of the mushroom extracts on liver cell DNA damage and on the initiation of liver carcinogenesis, respectively. Previous treatment with the highest concentration of A. blazei (11.5 mg/ml) significantly reduced DNA damage, indicating a protective effect against DEN-induced liver cytotoxicity/genotoxicity. However, the same dose of mushroom extract significantly increased the number of GST-P-positive liver foci

Aberrant crypt foci and colon cancer: comparison between a short- and medium-term bioassay for colon carcinogenesis using dimethylhydrazine in Wistar rats

Aberrant crypt foci (ACF) in the colon of carcinogen-treated rodents are considered to be the earliest hallmark of colon carcinogenesis. In the present study the relationship between a short-term (4 weeks) and medium-term (30 weeks) assay was assessed in a model of colon carcinogenesis induced by dimethylhydrazine (DMH) in the rat. Six-week-old male Wistar rats were given subcutaneous injections of DMH (40 mg/kg) twice a week for 2 weeks and killed at the end of the 4th or 30th week. ACF were scored for number, distribution pattern along the colon and crypt multiplicity in 0.1 percent methylene-blue whole-mount preparations. ACF were distinguished from normal crypts by their larger size and elliptical shape. The incidence, distribution and morphology of colon tumors were recorded. The majority of ACF were present in the middle and distal colon of DMH-treated rats and their number increased with time. By the 4th week, 91.5 percent ACF were composed of one or two crypts and 8.5 percent had three or more crypts, while by the 30th week 46.9 percent ACF had three or more crypts. Thus, a progression of ACF consisting of multiple crypts was observed from the 4th to the 30th week. Nine well-differentiated adenocarcinomas were found in 10 rats by the 30th week. Seven tumors were located in the distal colon and two in the middle colon. No tumor was found in the proximal colon. The present data indicate that induction of ACF by DMH in the short-term (4 weeks) assay was correlated with development of well-differentiated adenocarcinomas in the medium-term (30 weeks) assay

Absence of genotoxic effects of crude and refined red palm oil on mouse bone marrow cells

Red Palm Oil (RPO), extracted from fruits of Elaeis guineensis, is a complex mixture consisting of over 99 per cent glycerides and about 1 per cent non-glyceride compounds. Its orange-red colour is due to its high content of carotenoid pigments, mainly alpha- and beta-carotene. Based on the fact that palm oil is a rich source of provitamin A, and because it is largely consumed in North and Northeastern Brazil, we evaluated possible clastogenic and cytotoxic activities of this oil on mouse bone marrow cells in vivo, as well as the alpha- and beta-carotene content. The experiments were performed using samples of refined and crude palm oil, of which two different phases, supernatant, sediment, and the mixture of both, were tested. The animals were treated by gavage, at daily doses of 4.5 g/Kg, for five consecutive days, and killed 24 hours after the last treatment, for chromosome preparations. The negative control group was treated with corn oil. There was no statistically significant difference in the frequency of chromosomal aberrations and in mitotic index when the animals which received palm oil were compared with the negative control. The beta-carotene content was higher than that of alpha-carotene, and the supematant phase was the richest source of carotenoids. These findings suggest that RPO has no genotoxic effect.