direct extrapolation of animal data to humans cannot be used to predict absolute risk. Data derived in humans can produce patterns of risk which might well be of use (Brenner and others 1995), in that the endpoint remains the same but only the radiation dose/dose rate/quality changes.
Research has been conducted to determine whether the resistance to radon in Syrian hamsters relative to that in rats was related to delivered dose or induced damage at the same level of exposure (Khan and others 1995). Rats and Syrian hamsters were exposed at the same time, which resulted in exposure to the same radon level and dose, and the frequency of micronuclei as an indicator of radiation dose was measured in deep-lung fibroblasts. It was determined that the exposure-response relationship for radon-induced micronuclei per Jhm-3 (WLM) was higher in the Syrian hamster than in the rat. That suggests that the dose and damage to the lung cells were similar in the 2 species and that the amount of chromosomal damage initially induced might not be related directly to the differences in species sensitivity for the induction of lung-cancer. Combining research on cellular and molecular changes with whole-animal exposures could provide some understanding of the basis of species and strain differences; these differences eventually might be related to individual changes in sensitivity for the induction of cancer.
It is well established that ionizing radiation in general and alpha particles in particular produce a dose-dependent delay in progression through both the G2 and the G1 stages of the cell cycle (for example, Lucke-Huhle and others 1982; Kasten and others 1991). The G2 delay has been postulated to give the cell time to repair damage before entering into mitosis (Maity and others 1994). The G1 delay has been shown to depend on the function of the tumor-suppressor protein p53 (Kasten and others 1991) and to be controlled to some degree by Rb gene expression (White 1994). Tumor cells without p53 or with a mutated p53 have lost their ability to respond to cell-cycle arrest after exposure to gamma rays (White 1994). The molecular mechanisms associated with radiation-induced cell-cycle delay have been reviewed (Murnane 1995; Rowley 1996). Cell-cycle progression and delay constitute a multistep process that involves well-defined temporal and spatial changes in expression, phosphorylation, and complex interactions between the level and structure of proteins (Metting and Little 1995; Murnane 1995; Rowley 1996). The importance of DNA damage in producing cell-cycle delay response and the importance of the delay in repair of genetic and lethal damage have been demonstrated and reviewed for dividing mammalian cells (Murnane 1995).
The information available on the response of cells to high-LET radiation damage delivered in G0/G1 cells and in the role of cell-cycle delay in these cells as they move from G0 into a cycling stage is far from complete. Consequently,