Dose response of chromosome aberrations at very low dose range

Frequency of chromosome aberration is generally accepted as the most sensitive biomarkers of ionizing radiation. In case of the JCO critically accident, it was available to estimate the doses less than 50 mGy even after more than 2 weeks from the accident (Sasaki, et al., 2001). From the view points of daily radiation exposures, the world average of natural background radiation is 2.4mSv per year, the dose limit for radiation workers settled by radiation protection authority in Japan is 50mSv per year or 100mSv per 5 year, and the dose of round-trip from Narita to New York by international airline is about 0.1mSv. Therefore it would be the only method to detect the biological events even in the case of low dose or low dose rate radiation range such as natural background levels of radiation exposure, occupational exposure of radiation workers, cosmic radiation exposure in airlines and space ships, and diagnostic exposure. Moreover it is also suggested to be epidemiologically correlated with cancer incidences (eg. Bonassi, et al., 2008). Hence it is the very important marker not only to measure the magnitude of biological effects but also to assess the significance on health effects of low levels of ionizing radiation. The conventional method of chromosome aberration analysis for the person suspected to be exposed low level radiation is to score 1,000 metaphases of peripheral lymphocytes using microscopy. But because the widely accepted dose response relationship of dicentric + centric ring in low dose range is around 15-30/1,000 cells/Gy and the background ratio of those aberration is of the order of 1/1,000 cells, it is theoretically impossible to measure the effects of low dose radiation less than 100 mGy or it is very difficult to decrease the dose levels to be distinguished from background variations even when the number of metaphase increased (Lloyd, et al., 2006) unless exposure-unrelated base level of each person was known. Furthermore, there still remain some problems in the data based of the dose response relationship in very low dose range around 10mGy from in vitro exposure experiments. There are not so many data of direct measurement in this range but some show J-shape dose response curve which undergo beneath background level in around 10mGy range. Even the most reliable data which were obtained from6-country collaboration study (Lloyd,et al.,1992) also show flat from zero to around 10mGy. There seems to remain some bias such as laboratory differences and less number of metaphases counted in each laboratory as a consequence of sharing. As for laboratory differences, there is a report considering them in general which says reported background aberration ratios differ more than 100 times even when the results were narrowed down to ones of measurements of enough number of metaphases, more than 1,000 (Hayata, 1997). It should represent not the real variations but the difference of sample treatments and /or scoring technique. Thus there are a lot of difficulties to measure the frequencies of chromosome aberrations caused by low levels of ionizing radiation. Now we are trying to confirm this very low dose relationship by small number of observers with crosschecking and by using robot system for preparing lymphocyte chromosome and computer aided automatic metaphase finding system to count sufficient numbers of metaphase. We found we could observe fine linear dose response even from 10mGy. I would discuss the problems to assess the small effects of small dose of ionizing radiation such as low dose rate irradiation and high background radiaton area, and to investigate the relationship between such small effects and other environmental mutagens such as smoking.The 3rd Asian Chromosome Colloquiu