Genotoxic potential and in vitro tumour-promoting potential of 2-dodecylcyclobutanone and 2-tetradecylcyclobutanone, two radiolytic products of fatty acids.

The DNA-damaging and tumour-promoting effects of two 2-alkylcyclobutanones (2-ACBs), which are found in irradiated fat-containing foods, were investigated by use of the comet assay and in an azoxymethane (AOM)-induced colon-carcinogenesis study in rats, respectively. We conducted genotoxicity tests of 2-dodecylcyclobutanone (2-dDCB) and 2-tetradecylcyclobutanone (2-tDCB) according to the test guidelines for chemicals or drugs. In addition, a cell-transformation assay with Bhas 42 cells was performed to investigate their promoting potential in vitro. The Salmonella typhimurium mutagenicity assay (Ames test), conducted with five tester strains, revealed that neither 2-dDCB nor 2-tDCB possessed mutagenic activity. Moreover, both in the in vitro chromosomal aberration test on CHL/IU cells and the in vivo bone-marrow micronucleus test where mice were given 2-dDCB and 2-tDCB (orally, up to 2000 mg/kg bw/day), we did not detect any clastogenic effects. Furthermore, DNA strand-breaks were not detected in the in vitro comet assay with CHL/IU cells, and DNA adducts derived from 2-dDCB and 2-tDCB were not detected in the colon tissues of the mice used for the micronucleus tests, in rats from a repeated dose 90-day oral toxicity test (0.03% 2-tDCB in the diet), or in rats from the AOM-induced carcinogenesis study (0.025% 2-tDCB in the diet). An in vitro tumour-promotion assay with Bhas 42 cells revealed that the number of transformed foci increased significantly following treatment of cells in the stationary phase with 2-dDCB or 2-tDCB for 10 days. Our results indicate that neither 2-dDCB nor 2-tDCB were genotoxic chemicals. However, they exhibited promoting activity, at least in vitro, when Bhas 42 cells were continuously exposed to these chemicals at toxic doses.

In vitro clastogenicity and phototoxicity of fullerene (C(60)) nanomaterials in mammalian cells.

Carbon nanomaterials such as carbon nanotubes, graphene, and fullerenes (C(60)) are widely used in industry. Because of human health concerns, their toxic potential has been examined in vivo and in vitro. Here we used mammalian cells to examine the in vitro clastogenicity as well as the phototoxicity of C(60). While C(60) induced no structural chromosome aberrations in CHL/IU cells at up to 5mg/ml (the maximum concentration tested), it significantly induced polyploidy at 2.5 and 5mg/ml with and without metabolic activation. In BALB 3T3 cells, C(60) showed no phototoxic potential but the anatase form of titanium oxide did. Since insoluble nanomaterials cause polyploidy by blocking cytokinesis rather than by damaging DNA, we concluded that the polyploidy induced by C(60) in CHL/IU cells was probably due to non-DNA interacting mechanisms.

Leiomyosarcoma of the hypopharynx: a case report.

Cases of leiomyosarcoma in the head and neck are very rare with only four reports of a leiomyosarcoma originating in the hypopharynx. A rare case of leiomyosarcoma of the hypopharynx is described. A 62-year-old woman, who had experienced slight difficulty of swallowing and hoarseness, visited our hospital. A smooth-surfaced tumor was found extending from the postcricoid to an area in the left pyriform sinus, and the vocal cord on the left side was fixed. Imaging studies, including FDG-PET CT imaging showed the tumor in the postcricoid, but no distinguishable distant metastases. A total laryngectomy with a left-lobe thyroidectomy was performed. Since no metastases of the regional lymph nodes were found by imaging, a neck dissection was not performed. Dense infiltration by spindle-shaped and/or round-like cells was observed histologically as the predominant growth pattern. In immunohistochemical staining, the tumor was positive for desmin and muscle actin, while it was negative for myoglobin, myogenin, cytokeratin, and S-100 protein. Electron microscopic examination did not show Z banding and sarcomeres. Those features lead to the diagnosis of a leiomyosarcoma. No recurrence has been found at 1 year after the surgery. Immunohistochemical staining and electron microscopic examination are essential for a definite diagnosis of leiomyosarcoma.