Challenging the assumptions

chemicals and ionizing radiation. While an earlier study by other researchers did not find any correlation between increased placental UGT activity and maternal cigarette smoking, this study found a strong correlation for mothers who were both drug abusers and smokers. This suggests that illicit drugs compound the problems associated with smoking. The study also reports the discovery of a previously unknown placental biochemical marker activity. Among maternal drug abusers, P1OH correlated consistently with ECOD activity but not with EROD activity. However, P1OH correlated with EROD or testosterone hydroxylase activity only among the-cigarette smoking controls. The authors suggest that because ECOD and EROD activity always exhibit a positive correlation in normal cigarette smoking conditions., this may be evidence that in normal conditions a "silent" cytochrome P450 gene form may be responsible for P1OH activity. This change in the steroid metabolism profile in vitro suggests that maternal drug abuse may alter normal hormonal balance during pregnancy. The use of illicit drugs by pregnant women may disrupt placental metabolism and exacerbate the effects of smoking. The authors suggest that these findings may mean that the combination of illicit drugs with certain prescribed medications could also complicate the expression of placental metabolizing enzymes. They urge that term placentas from mothers using any medication or illicit drug be evaluated after delivery in terms of total metabolizing activity in vitro and any possible link to adverse responses in later development of the infant. For decades, scientists have agreed that cancer risks are best estimated by extrapolating from the high-dose effects observed in a cohort of atomic bomb survivors over the course of the subjects' lives. In this issue, Alice Stewart, a retired professor of epidemiology from the University of Birmingham in Great Britain, questions the traditional assumptions used to form cancer risk assessments: namely, that the only late effect of radiation is cancer, that there is no cancer risk at the radiation levels typically faced by nuclear workers, that the risk for leukemia far exceeds that for solid tumors, and that radiosensitivity is higher at the beginning of adult life than at the end [EHP 108:93-96]. Stewart also presents the alternative view that, in addition to cancer, high-dose exposures to radiation may also result in irreversible damage to the immune system. New research using a cohort of atomic bomb survivors questions how assessments of cancer risk from radiation exposure are made. Stewart's views challenge the assumptions …

The authors suggest that these findings may mean that the combination of illicit drugs with certain prescribed medications could also complicate the expression of placental metabolizing enzymes. They urge that term placentas from mothers using any medication or illicit drug be evaluated after delivery in terms of total metabolizing activity in vitro and any possible link to adverse responses in later development of the infant. -John S. Manuel

Risk of Effects from Radiation
For decades, scientists have agreed that cancer risks are best estimated by extrapolating from the high-dose effects observed in a cohort of atomic bomb survivors over the course of the subjects' lives. In this issue, Alice Stewart, a retired professor of epidemiology from the University of Birmingham in Great Britain, questions the traditional assumptions used to form cancer risk assessments: namely, that the only late effect of radiation is cancer, that there is no cancer risk at the radiation levels typically faced by nuclear workers, that the risk for leukemia far exceeds that for solid tumors, and that radiosensitivity is higher at the beginning of adult life than at the end [EHP 108:93-96]. Stewart also presents the alternative view that, in addition to cancer, high-dose exposures to radiation may also result in irreversible damage to the immune system. New research using a cohort of atomic bomb survivors questions how assessments of cancer risk from radiation exposure are made.
Stewart's views challenge the assumptions behind the radiation risk coefficients (or slope factors) espoused by the National Academy of Sciences' Committee on the Biological Effects of Ionizing Radiation and the International Commission on Radiological Protection. These coefficients are based on analyses of life span study (LSS) data gathered by the Radiation Effects Research Foundation in Hiroshima, Japan, which concluded repeatedly that the LSS cohort was homogeneous and representative of the general population.
Stewart and colleagues discovered that the noncancer death rate in the LSS cohort was lower in the middle of the dose range than at either extreme, prompting them to perform an independent analysis. This analysis, published in the March 1998 issue of the European Jlournal of Oncology, revealed significant differences between survivors with and without acute injuries such as burns. It also showed that only in a small group of survivors with multiple injuries was the leukemia death rate higher than normal, and only in a much larger group of survivors with no acute injuries was the cancer death rate exceptionally high among people exposed as young adults. Based on this assessment, Stewart concludes that thousands of early deaths from acute effects of immune system damage left the LSS cohort biased toward those who were exceptionally resistant to late effects of radiation. Furthermore, because many early deaths may have been incorrectly attributed to causes other than immune system damage, it was not a homogeneous population, nor was it representative of the general population.
Turning to the effects of low-dose exposures, Stewart reviewed the Oxford Survey of Childhood Cancers, which was the first survey to find evidence of a cancer risk at low-dose levels, and earlier studies by herself and colleagues that first found evidence of a cancer risk for nuclear workers at the Hanford Nuclear Site in Washington State. Based on her assessment of both studies, Stewart concludes that the risk of leukemia is not exceptionally high following low-dose exposures and that childhood cancers are typically the result of in utero mutations that have teratogenic as well as carcinogenic effects. She also concludes that the low cancer death rates found at Hanford resulted from the selective recruitment of exceptionally healthy individuals into the nuclear industry. Stewart notes that a new methodology in which the annual dose of each worker contributes separately to the total risk has identified a cancer risk among Hanford nuclear workers. Furthermore, Stewart found that sensitivity to carcinogenic effects of radiation is increased in young embryos and in people over 50.