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Versitat Munster. the Production of Single Strand Breaks

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Versitat Munster. the Production of Single Strand Breaks ABSTRACTS OF PROFFERED PAPERS 757 WuBKER, Institut fiir Strahlenbiologie, Uni­ experiment (3Fj4D) was studied. Bleomycin versitat Munster. was found to apparently decrease, by about The production of single strand breaks 30%, the repair of sublethal radiation (SSBs) and double strand breaks (DSBs) in damage when given simultaneously with the T 2 DNA (16 ttgfml) by bleomycin (Bl) radiation exposure (5 mgfkg). (40 ttgfml) was investigated quantitatively. At 5°C 0·11 SSBjmin per T 2 genom were found. The addition of 1 mmol cysteamine RADIATION AND ANTI-TUMOUR (SH) enhances the single strand breakage rate DRUGS. M. BARKER-GRIMSHAW, K. HELL­ by a factor of 25. DSBs were found at a rate MANN and G. E. MuRKIN, Chemotherapy of 0·5/min only in the presence of SH and Bl. Department, Imperial Cancer Research Fund, Since the accidental DSB rate due to SSBs in London. opposite DNA strands is less than I0- 3jmin Growth inhibitory effects of the anti­ per T 2 genom DSBs must be produced tumour drugs 5-fl.ourouracil, adriamycin, directly by the action of Bl. The obtained hydroxyurea, bleomycin, cyclophosphamide, DNA profiles did not follow a random methotrexate, ICRF 159 and 593A and the distribution; thus bleomycin apparently acts radiosensitizer Ro-07-0582 combined with a at specific sites along the T 2 genom. X­ standard dose of radiation was tested on the irradiation followed by Bl-SH treatment radiosensitive sarcoma 180. The most effec­ resulted in an increased DNA degradation. tive potentiators were 593A and ICRF 159. The number of SSBs is at least 3 times larger They were then examined against the than expected if the effect of both treatments relatively radioresistant Lewis lung carcinoma is just additive. and melanoma B16 using either single doses of drug and radiotherapy or the same total dose given in fractions over 5 days. 593A MODIFICATION OF THE RESPONSE was equally potent whether given as a single OF MOUSE SKIN TO X-IRRADIA­ maximum tolerated dose or in divided doses; TION BY BLEOMYCIN TREATMENT. ICRF 159 was ineffective when given as a J. T. LEITH and B. S. LEWINSKY, Lawrence single low dose (though it was effective given Berkeley Laboratory, University of California. in a single high dose), but highly effective in Skin reactions occurring on the legs of divided low doses. Clinical trials with mice after 230 kV x-irradiation were used to ICRF 159 in combination with radiotherapy investigate the combined effects of x-irradia­ are in progress. tion and bleomycin. Bleomycin was given daily for 5 days (5 mgfkgjday), either pre­ ceding or following graded single doses of EFFECT OF LUCANTHONE ON THE x-rays. Skin reactions occurring after com­ RADIOSENSITIVITY OF A MOUSE bined treatment were compared with skin TUMOUR. K. R. RAo and H. FRITZ­ reactions produced by x-irradiation alone. NIGGLI, Radiobiology Institute of Zurich Both bleomycin schemes yielded average University. 1-30 day post-irradiation skin reactions Lucanthone is reported to be carcinostatic greater than skin reactions seen after x­ (Hirschberg et al., J. natn. Cancer Inst., 1959, irradiation alone. Dose-response curves for 22, 567) and a radiosensitizer (Bases, Cancer the combined treatments were parallel to the Res., 1970, 30, 2007). But in our study x-irradiation alone treatment, but were dis­ lucanthone alone (70 mgjkg body weight) had placed upwards. The responses obtained in no lasting effect on the Ehrlich carcinoma in the 2 bleomycin schemes were not signifi­ mice. Based on mitotic studies, 4-day old cantly different. The dose modifying effect ascites tumour was not sensitized to x-rays of the bleomycin treatments ranged from when pretreated with lucanthone. Tumour 1·5 at low levels of effect to 1·2 at higher growth, evaluated as the average weight of levels of effect. It is concluded that the solid tumours or the number of tumour cells combined effects of bleomycin and x-irradia­ in ascites bearing mice, was not significantly tion in this design were additive. In a second different between the group treated with series of experiments, the ability of bleomycin x-rays only and the one treated with lucan­ to affect the ability of mouse skin to recovery thane plus x-rays. Thus, lucanthone seems to from radiation injury in a fractionated enhance the radiosensitivity of normal cell .
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