Male and female CDF1 mice were administered a single oral dose of 3 mumol of the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) or 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and killed 24 h later. DNA was isolated from the livers, lungs, kidneys, colon and forestomach and analysed by 32P-postlabelling for the presence of IQ and MeIQ adducts. Several adduct-enrichment procedures were investigated, including ATP-deficient labelling conditions, butanol extraction and nuclease P1 digestion, and only the ATP-deficient procedure was found to produce the same adduct pattern on polyethyleneimine--cellulose TLC as the standard procedure. Up to nine adduct spots were detected in liver DNA from IQ-treated mice, two of which were not detected in other tissues. The levels of binding in both male and female mice were in the order liver greater than kidney greater than colon greater than forestomach greater than lung. Analysis of DNA from MeIQ-treated mice revealed the presence of up to seven adducts, one of which was detected in liver but not in other tissues. The relative order of DNA binding was kidney greater than liver greater than or equal to colon greater than forestomach greater than lung. As dietary feeding of IQ induces liver, lung and forestomach tumours, and MeIQ induces liver and forestomach tumours in this mouse strain, these binding levels do not correlate with the susceptibility of the organs to carcinogenesis induced by these compounds; the results may indicate the importance of additional factors in determining organ specificity of carcinogenicity.
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http://dx.doi.org/10.1093/carcin/11.6.1005 | DOI Listing |
Int J Mol Sci
July 2024
Experimental Clinical Oncology-Department of Oncology, Aarhus University Hospital, DK-8200 Aarhus, Denmark.
This pre-clinical study was designed to demonstrate how vascular disrupting agents (VDAs) should be administered, either alone or when combined with radiation in clinically relevant fractionated radiation schedules, for the optimal anti-tumor effect. CDF1 mice, implanted in the right rear foot with a 200 mm murine C3H mammary carcinoma, were injected with various doses of the most potent VDA drug, combretastatin A-1 phosphate (CA1P), under different schedules. Tumors were also locally irradiated with single-dose, or stereotactic (3 × 5-20 Gy) or conventional (30 × 2 Gy) fractionation schedules.
View Article and Find Full Text PDFFront Oncol
July 2024
Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark.
Objective: A favorable effect of ultra-high dose rate (FLASH) radiation on normal tissue-sparing has been indicated in several preclinical studies. In these studies, the adverse effects of radiation damage were reduced without compromising tumor control. Most studies of proton FLASH investigate these effects within the entrance of a proton beam.
View Article and Find Full Text PDFInt J Radiat Oncol Biol Phys
September 2024
Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
Purpose: The aim of this work was to investigate the ability of a biological oxygen enhancement ratio-weighted dose, D, to describe acute skin toxicity variations observed in mice after proton pencil beam scanning irradiations with changing doses and beam time structures.
Methods And Materials: In five independent experiments, the right hind leg of a total of 621 CDF1 mice was irradiated previously in the entrance plateau of a pencil beam scanning proton beam. The incidence of acute skin toxicity (of level 1.
Acta Oncol
November 2023
Experimental Clinical Oncology-Dept. Oncology, Aarhus University Hospital, Aarhus, Denmark.
Background: The benefit of combining immunotherapy with photon irradiation has been shown pre-clinically and clinically. This current pre-clinical study was designed to investigate the anti-tumour action of combining immunotherapy with protons.
Materials And Methods: Male CDF1 mice, with a C3H mammary carcinoma inoculated on the right rear foot, were locally irradiated with single radiation doses when tumours reached 200mm.
J Appl Physiol (1985)
March 2023
Experimental Clinical Oncology, Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
The objectives of this study were to investigate ) the effect of acute aerobic exercise on tumor hypoxia and blood perfusion, ) the impact of exercise intensity, ) the duration of the effect, and ) the effect of prolonged training on tumor hypoxia and tumor growth. Female CDF1 mice were inoculated with the C3H mammary carcinoma either in the mammary fat pad or subcutaneously in the back. For experiments on the effect of different intensities in a single exercise bout, mice were randomized to 30-min treadmill running at low-, moderate-, or high-intensity speeds or no exercise.
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