Compensation techniques in NIRS proton beam radiotherapy.

Proton beam has the dose distribution advantage in radiation therapy, although it has little advantage in biological effects. One of the best advantages is its sharp fall off of dose after the peak. With proton beam, therefore, the dose can be given just to cover a target volume and potentially no dose is delivered thereafter in the beam direction. To utilize this advantage, bolus techniques in conjunction with CT scanning are employed in NIRS proton beam radiation therapy planning. A patient receives CT scanning first so that the target volume can be clearly marked and the radiation direction and fixation method can be determined. At the same time bolus dimensions are calculated. The bolus frames are made with dental paraffin sheets according to the dimensions. The paraffin frame is replaced with dental resin. Alginate (a dental impression material with favorable physical density and skin surface contact) is now employed for the bolus material. With fixation device and bolus on, which are constructed individually, the patient receives CT scanning again prior to a proton beam treatment in order to prove the devices are suitable. Alginate has to be poured into the frame right before each treatments. Further investigations are required to find better bolus materials and easier construction methods.

Washout measurement of radioisotope implanted by radioactive beams in the rabbit.

Washout of 10C and 11C implanted by radioactive beams in brain and thigh muscle of rabbits was studied. The biological washout effect in a living body is important in the range verification system or three-dimensional volume imaging in heavy ion therapy. Positron emitter beams were implanted in the rabbit and the annihilation gamma-rays were measured by an in situ positron camera which consisted of a pair of scintillation cameras set on either side of the target. The ROI (region of interest) was set as a two-dimensional position distribution and the time-activity curve of the ROI was measured. Experiments were done under two conditions: live and dead. By comparing the two sets of measurement data, it was deduced that there are at least three components in the washout process. Time-activity curves of both brain and thigh muscle were clearly explained by the three-component model analysis. The three components ratios (and washout half-lives) were 35% (2.0 s), 30% (140 s) and 35% (10 191 s) for brain and 30% (10 s), 19% (195 s) and 52% (3175 s) for thigh muscle. The washout effect must be taken into account for the verification of treatment plans by means of positron camera measurements.

Modification of enzyme sulfhydryl groups suppresses UV-induced mutagenesis depending on the nucleotide excision repair system in Escherichia coli B/r WP2.

S-Methyl methanethiosulfonate (MMTS), which was isolated from cauliflower (Brassica oleracea var. botrytis) homogenate as a potent bio-antimutagen, has been used as an enzyme-sulfhydryl (SH) temporary blocking agent in modification studies of enzyme activities. We examined whether 23 kinds of MMTS-related compounds have a suppressing effect on UV mutagenesis in Escherichia coli B/r WP2. Disulfide derivatives of diphenyl, 2.2'-dipyridine and 4.4'-dipyridine, and N-ethyl maleimide (NEM), which temporarily or tightly block sulfhydryl (SH)-groups, showed similar suppressing effect in E. coli B/r WP2, but not in WP2s hcr- (uvrA-) in the range of nanomolar/plate as MMTS previously did. Cystamine sulfate, methyl methylsulfinylmethyl sulfide and S-methyl-L-cysteinesulfoxide moderately suppressed, and diallyl disulfide and glutathione (oxidized form) weakly suppressed UV mutagenesis in E. coli B/r WP2 in the range of micromolar/plate. MMTS and phorone, a glutathione (GSH)-depleting agent, lowered the intracellular GSH level in E. coli B/r WP2, but phorone did not inhibit UV-induced mutation. These results indicate that the target for SH-modification is enzyme-SHs but not GSH, and that the direct or indirect modification of enzyme-activity by SH-blocking might be involved in the antimutagenesis through a pathway associated with the DNA-excision repair system.

Suppressing effects of S-methyl methanethiosulfonate and diphenyl disulfide on mitomycin C-induced somatic mutation and recombination in Drosophila melanogaster and micronuclei in mice.

S-Methyl methanethiosulfonate (MMTS) and diphenyl disulfide (DPDS) are temporary enzyme-sulfhydryl blocking agents. They are naturally occurring phytoalexin-like and synthetic substances known to be very potent bio-antimutagens in Escherichia coli B/r WP2. In the present paper, the suppressing effects of MMTS on mitomycin C (MMC)-induced mutant wing spots in the somatic mutation and recombination test (SMART) of Drosophila melanogaster, and of MMTS and DPDS on MMC-induced micronucleated peripheral reticulocytes are described. MMTS consistently reduced the numbers of MMC-induced small single, large single and twin spots per wing at a dose of 10-1000 micrograms/vial, in a dose-dependent manner. MMTS reduced the number of twin spots per wing on the spontaneous mutation at the dose of 1000 micrograms/vial. MMTS and DPDS dose-dependently reduced the frequencies of MMC-induced micronucleated peripheral reticulocytes at a dose of 10-40, and 3-100 micrograms/kg, respectively. Our results confirmed that enzyme-sulfhydryl blocking agents, such as MMTS and DPDS, are effective antimutagens in vivo too.

High-dose-rate remote afterloading intracavitary radiation therapy for cancer of the uterine cervix. A 20-year experience.

Retrospective analysis was performed on 1022 patients with squamous cell carcinoma of the uterine cervix who were treated with high-dose-rate remote afterloading intracavitary irradiation at the National Institute of Radiological Sciences, Angawa, Chiba-shi, Japan, from 1968 to 1982 in comparison with low-dose-rate intracavitary radiation therapy. The patient population consisted of 147 patients with Stage I disease, 256 patients with Stage II disease, 515 patients with Stage III disease, and 104 patients with Stage IV disease. Absolute 5-year survival rates for Stages Ib, IIa, IIb, IIIb, IVa, and IVb disease were 88.1%, 76.9%, 67.0%, 52.2%, 24.1%, and 13.3%, respectively. The rates of severe complication of Grades 3 and 4 were 4.1% for the rectosigmoid colon, 1.2% for the bladder, and 1.1% for the small intestine. In the case of Stage I to II disease, the optimal dose from intracavitary sources was suggested to be 2900 cGy +/- 200 cGy at point A, with 4 to 5 fractions of 600 to 700 cGy delivered over 4 to 5 weeks. These results suggested that high-dose-rate intracavitary radiation therapy provided clinical results comparable to those of a low-dose-rate technique.

S-methyl methanethiosulfonate, bio-antimutagen in homogenates of Cruciferae and Liliaceae vegetables.

The isolation of a new type of bio-antimutagen, S-methyl methanethiosulfonate (MMTS), from cauliflower (Brassica oleracea var. botrytis) and the distribution and formation of MMTS in Cruciferae and Liliaceae vegetables are described. For the separation and purification, cauliflower curds were homogenized, extracted with acetone, and then purified by organic solvent extraction and by various processes of chromatographic separation. The chemical structure of an active principle was identified as MMTS by GC-MS and 1H-NMR analyses. MMTS was widely found in vegetable homogenates of the Cruciferae and Liliaceae species, and is found from its precursor S-methyl-L-cysteinesulfoxide (SMCS), by wounding the vegetable tissues. Wounding may induce C-S lyase, which converts SMCS to MMTS. The amount of MMTS formed was affected by the pH value for C- lyase, but not by the SMCS content in a tissue homogenate.

Suppressive effects of S-methyl methanethiosulfonate on promotion stage of diethylnitrosamine-initiated and phenobarbital-promoted hepatocarcinogenesis model.

Modifying effects of S-methyl methanethiosulfonate (MMTS) on diethylnitrosamine (DEN)-initiated and phenobarbital (PB)-promoted hepatocarcinogenesis were examined in rats. Five-week-old male F344 rats were divided into 8 groups. After a week, groups 1-5 were given DEN (100 mg/kg body weight, i.p.) once a week for 3 weeks, whereas groups 6-8 received vehicle treatment. Group 2 was given 100 ppm MMTS containing diet in the initiation phase. From 4 weeks after the start of experiment, groups 3 and 5 were fed MMTS, and groups 1-3 and 7 received drinking water containing 500 ppm PB. Group 6 was given MMTS diet alone throughout the experiment (24 weeks). The incidences of hepatocellular adenoma and total liver tumors were significantly smaller in group 3 than those of group 1. The average numbers of hepatocellular adenoma, carcinoma and total tumors in group 3 were significantly smaller than in group 1. Glutathione S-transferase placental form-positive foci were also significantly decreased by MMTS treatment in the promotion phase. MMTS treatment in the initiation or promotion phase reduced ornithine decarboxylase activity in the liver of rats given DEN. The antioxidant activity against lipid peroxidation of MMTS was confirmed in tests with rabbit erythrocyte membrane ghosts or rat hepatocytes. These results suggest that MMTS is a promising chemopreventive agent for liver neoplasia when concurrently administered with PB.