Water soluble vitamin E (TMG) as a radioprotector.

Tocopherol monoglucoside (TMG), a water soluble derivative of vitamin E offers protection against deleterious effects of ionizing radiation, both under in vivo and in vitro conditions, to biological systems. TMG was found to be a potent antioxidant and an effective free radical scavenger. It forms a phenoxyl radical similar to trolox upon reaction with various one-electron oxidants. TMG protected DNA from radiation-induced strand breaks. It also protected thymine glycol formation induced by gamma-radiation. Gamma-radiation-induced loss of viability of EL-tumor cells and peroxidation of lipids in microsomal and mitochondrial membranes were prevented by TMG. TMG was nontoxic to mice when administered orally up to 7.0 g/kg body weight. The LD50 dose of TMG for ip administration in mice was 1.15 g/kg body wt. In rats, following oral and ip administration of TMG, the absorption (distribution) half lives were 5.8 and 3.0 min respectively and elimination half lives were 6.7 and 3.1 min respectively. Embryonic mortality resulting from exposure of pregnant mice to ionizing radiation (2 Gy) was reduced by 75% by ip administration of TMG (0.6 g/kg, body wt) prior to irradiation. TMG offered protection to mice against whole body gamma-radiation-induced lethality and weight loss. The LD50(30) of mice increased from 6 to 6.72 Gy upon post irradiation administration of a single dose of TMG (0.6 g/kg, body wt) by ip.

Clinical outcome of intraoperative pelvic hyperthermochemotherapy for patients with Dukes' C rectal cancer.

In attempts to prevent local recurrence after curative resection for rectal cancer, intraoperative pelvic hyperthermochemotherapy (IOPHC) was prescribed for 27 patients with Dukes' C cancer. The procedures used were as follows: immediately after amputation or resection of the rectum with extended lymphadenectomy, the pelvic cavity was filled with physiological saline containing 40 micrograms/ml mitomycin C, which was warmed at 45 degrees C for 90 min with an apparatus devised for IOPHC. Thirty-five patients who underwent surgery alone for Dukes' C rectal cancer within the same period served as controls. There was a local recurrence in three patients in the IOPHC group (11.1%), and in 13 in the control group (37.1%). With regard to hepatic or pulmonary metastasis, there was no difference between the two groups. There was no morbidity in the IOPHC treatment except for a large volume of exudate from the pelvic cavity. Thus, IOPHC can be considered as one option for limiting local recurrence after surgical resection of an advanced rectal cancer.

Hyperthermia-induced antitumor activity in human gastric cancer cells serially transplanted into nude mice.

Hyperthermia-induced antitumor activity was assessed histopathologically and findings related to transplantation of human gastric cancer into nude mice were examined. Fragments of human gastric cancer were incubated at 37 degrees C to 47 degrees C for various durations of time, then were evaluated either histologically or with regard to delay in tumor growth and the rates of transplantation into nude mice. Fragments exposed to 39 degrees C for 30 min to 120 min and 41 degrees C for 30 min did not differ from findings in the controls concerning tumor growth and transplantability. In the case of 41 degrees C for 60 min or more, the rates of transplantation decreased significantly and there was a delay in tumor growth. At 43 degrees C for 120 min, 45 degrees C for 30 and 60 min, and 47 degrees C for 15 to 60 min, transplantability was nil. In the groups with a delay in tumor growth, there were irreversible changes in nucleic and cytoplasmic components, and in 6 groups with no evidence of transplantability, complete destruction of the glandular structure, pyknosis and karyorrhexis as well as disappearance of the cytoplasm occurred in almost all cases. Thus, the thermal dose of 43 degrees C for 120 min seems to be the minimally effective one for hyperthermia-induced tumoricidal activity.