Abstract
The interactions of radiation and adriamycin (ADM), bleomycin (BLM), mitomycin C (MM-C), or cis-diamminedichloroplatinum II (cis-DDP) in mouse jejunal crypt cells were studied using the microcolony survival assay. ADM administered from 24 h before to 48 h after irradiation resulted in an almost constant enhancement of the radiation response, the dose effect factor (DEF) being 1.19. The effect of BLM was extremely dependent on the sequence and interval between drug administration and irradiation. The most pronounced effect was observed when BLM was given 2 h before irradiation (DEF = 2.40), at which interval the D0 surprisingly increased by a factor of 1.4. Administration of MM-C from 24 h before to 24 h after irradiation enhanced the radiation response. The effect peaked on administration 6 h before irradiation (DEF = 1.21) and diminished by application after irradiation. Cis-DDP enhanced the radiation response only when given before irradiation resulting in a DEF of 1.23 and a decreased D0.
Highlights
Unanaesthetized male C3D2F,/Bom mice (C3H/Tify x DBA/2,S), 9-12 weeks of age, with good access to air were exposed to single-dose whole-body irradiation with a 250 kV Muller X-ray unit as previously described
The other drugs did not influence the crypt number scored at the specified regeneration times
The survival curves for radiation alone and for ADM administered 15 min before irradiation are shown in dose effect factor (DEF) and isodose effect ratio (IER) were 1.19 and 5.5, respectively
Summary
Unanaesthetized male C3D2F,/Bom mice (C3H/Tify x DBA/2,S), 9-12 weeks of age, with good access to air were exposed to single-dose whole-body irradiation with a 250 kV Muller X-ray unit as previously described (von der Maase, 1984a). Mitomycin C (MM-C) and cis-diamminedichloroplatinum II (cis-DDP) were kindly provided by Bristol-Myers A/S, adriamycin (ADM) by Farmitalia, Carlo Erba, and bleomycin (BLM) by H. Each drug was applied at the maximum tolerated dose (MTD), equivalent to the dose that would kill - 1% of the mice within 60 days. The MTDs were estimated as previously described (von der Maase, 1984a). BLM was dissolved in isotonic saline and the other drugs in sterile distilled water. All drugs were administered intraperitoneally as single doses at a constant volume of 0.02 ml g1 body wt
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