The combined effect of bleomycin and irradiation on mouse lip mucosa. 2. Influence on the accumulation and repair of sublethal damage during fractionated irradiation.
The effect on the mouse lip mucosa of different fractionated irradiation schedules (with respectively 1, 2, 4 10 and 20 equal fractions) with and without a simultaneous constant drug regimen (bleomycin 40 mg/kg in a continuous subcutaneous infusion over seven days) was investigated. Lowering the fraction size resulted in a progressive increase of both the dose modification factors (DMF) and the absolute dose reduction (ADR), i.e. from 1.19 and 2.8 Gy respectively for single doses to 1.86 and 21.5 Gy respectively for 20 fractions (at isoeffect level 3.5). The mechanisms involved are most probably a direct cell kill by bleomycin, together with a reduced capacity to accumulate and/or to repair sublethal damage, although the influence of redistribution in the cell cycle during bleomycin infusion can not be excluded. Such large differences in the interaction between chemotherapy and irradiation as a function of the fractionation schedule could lead to a significant underestimate of response if data from single dose or 2-fraction experiments are extrapolated to regimens used in clinical practice.
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007700:Kinetics; D008046:Lip / Q000187:drug effects* / Q000528:radiation effects; D051379:Mice; D008815:Mice, Inbred Strains; D009061:Mouth Mucosa / Q000187:drug effects* / Q000528:radiation effects; D013997:Time Factors
D001761:Bleomycin