Lung tumour risk in radon-exposed rats from different experiments: comparative analysis with biologically based models.
Data sets of radon-exposed male rats from Wistar and Sprague-Dawley strains have been investigated with two different versions of the two-step clonal expansion (TSCE) model of carcinogenesis. These so-called initiation-promotion (IP) and initiation-transformation (IT) models are named after the cell-based processes that are assumed to be induced by radiation. The analysis was done with all malignant lung tumours taken to be incidental and with fatal tumours alone. For all tumours treated as incidental, both models could explain the tumour incidence data equally well. Owing to its better fit, only the IP model was applied in the analysis of fatal tumours that carry additional information on the time when they cause death. A statistical test rejected the hypothesis that a joint cohort of Wistar and Sprague-Dawley rats can be described with the same set of model parameters. Thus, the risk analysis has been carried out for the Wistar rats and the Sprague-Dawley rats separately and has been restricted to fatal tumours alone because of their similar effect in humans. Using a refined technique of age-adjustment, the lifetime excess absolute risk has been standardised with the survival function from competing risks in the control population. The age-adjusted excess risks for both strains of rats were of similar size, for animals with first exposure later in life they decreased markedly. For high cumulative exposure the excess risk increased with longer exposure duration, for low cumulative exposure it showed the opposite trend. In addition, high cumulative exposure exerted lethal effects other than lung cancer on the rats.
Kaiser
J C
JC
Institute of Radiation Protection, GSF--National Research Center for Environment and Health, 85764 Neuherberg, Germany. christian.kaiser@gsf.de
Heidenreich
W F
WF
Monchaux
G
G
Morlier
J P
JP
Collier
C G
CG
D000280:Administration, Inhalation; D000367:Age Factors; D000375:Aging; D000396:Air Pollutants, Radioactive / Q000009:adverse effects*; D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D004195:Disease Models, Animal; D005260:Female; D015994:Incidence; D008175:Lung Neoplasms / Q000209:etiology*; D008297:Male; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000209:etiology; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D011886:Radon / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D000396:Air Pollutants, Radioactive; D011886:Radon