Bromodichloromethane induces cell proliferation in different tissues of male F344 rats by suppression of E-cadherin expression via hypermethylation or transcriptional activation of c-myc and cyclin D1.

The aim of this study was to investigate the mechanism of bromodichloromethane (BDCM) - induced cell proliferation in different tissues of male F344 rats. Rats were administered at doses of 0 and 100mg/kg/day BDCM dissolved in corn oil by gavage for 5 days/week for 1, 4, 8 and 12 weeks. Then the colon, kidney and liver were collected. No histologic lesions were observed in the colon of rats exposed to BDCM, while there were mild nephrotoxicity and marginal hepatotoxicity related to BDCM treatment. Moreover, BDCM enhanced cell proliferation in the colon and kidney but not in the liver. In colons, hypermethylation in E-cadherin promoter might be associated with inhibition of mRNA and protein expression after 12 weeks of BDCM exposure. In kidneys, BDCM decreased E-cadherin mRNA expression, accompanying with transcriptional activation of c-myc and cyclin D1. However, suppression of E-cadherin mRNA and protein expression occurred in the absence of significant changes in DNA methylation. Therefore, suppression of E-cadherin expression via hypermethylation or transcriptional activation of c-myc and cyclin D1 may be involved in BDCM-induced cell proliferation in different tissues of male F344 rats.

Extract of Toxicodendron quercifolium caused genotoxicity and antigenotoxicity in bone marrow cells of CD1 mice.

As has been shown in numerous studies, naturally occurring compounds can have protective effects towards mutagens and carcinogens. In the present study, the genotoxic/antigenotoxic effect of Toxicodendron quercifolium (poison ivy) extract, which has been identified as antigenotoxic in human HepG2 cells in former studies, was examined in the in vivo micronucleus assay using polychromatic erythrocytes (PCE) of bone marrow of CD1-mice. For this, D0 (1:10), D0 (1:25), D0 (1:50), D1 (1:50), D2 (1:50), and D4 (1:50) dilutions of ethanolic plant extract prepared on the basis of the "Hömoopathisches Arzneimittelbuch (HAB 2000)" were administered orally to CD1 mice over a period of two days. A significant increase (p < 0.05) in micronucleus frequencies was found after administration of D0 (1:10), the highest tolerated dose. Additionally, antigenotoxic effects of T. quercifolium towards benzo(a)pyrene-induced micronucleus formation were studied. For that, four dilutions of the plant extract [D0, D2, D4, D6, each 1:50] were administered orally to CD1 mice for five days prior to the administration of benzo(a)pyrene (250 mg/kg b.w.) for another two days. It was found that the administration of the dilutions D0 (1:50) and D2 (1:50) of T. quercifolium extract significantly inhibited benzo(a)pyrene-induced micronucleus formation (p < 0.0001). The results of this study indicated that T. quercifolium extract has the character of a so-called "Janus"-genotoxin: High doses led to a weak but significant increase of micronucleus frequencies whereas low doses showed chemopreventive effects towards benzo(a)pyrene-induced DNA damage. The constituents of T. quercifolium responsible for the genotoxic and antigenotoxic effects may be flavonoids, which are known to have prooxidative and scavenging effects and identified by HPLC-MS/MS.

[Effects of selenium on benzo[a] pyrene-induce DNA damage in mouse lung cells].

OBJECTIVE: To explore the effects of selenium on DNA damage induced by benzo[a] pyrene (BaP) in mouse lung cells. METHODS: Sodium selenite was given to Kunming male mice by i.p. and BaP was given by oral gavage. The control group was given solvent only with the same method. DNA damage was detected by single cell gel electrophoresis (or comet assay). RESULTS: The damage degrees in mice treated with 125, 250 and 500 mg/kg of BaP were more severe than that of control (P < 0.01). The rates of comet cells in the BaP-treated groups (43.50%, 84.00%, 95.63%) were significantly higher than that of control (9.75%, P < 0.01), and there was obvious dose-response relationship. 0.75, 1.50 and 3.00 mg/kg of sodium selenite presented antagonistic effects against DNA damage induced by 250 mg/kg of BaP in mouse's lung cells. The antagonistic effect of sodium selenite at the dose of 1.50 mg/kg was better than those of sodium selenite at the doses of 0.75, 3.00 mg/kg. CONCLUSION: BaP at the doses of 125 approximately 500 mg/kg could significantly induce DNA damage of lung cells in mice. 0.75 approximately 3.00 mg/kg of sodium selenite could inhibit DNA damage of lung cells in mice induced by 250 mg/kg of BaP.