Faculty Bibliography

About 2,650 persons who received X-ray treatment for purported enlarged thymuses in infancy and 4,800 sibling controls have been followed by mail questionnaire for an average of 29 years to observe their incidence of thyroid tumors. The follow-up rate in the latest survey was 88% in both groups. The radiation doses to the thyroid gland ranged from 5 to over 1,000 rad, with 62% receiving less than 50 rad. To date 30 thyroid cancers and 59 benign thyroid adenomas have been detected in the irradiated group, as compared with 1 thyroid cancer and 8 adenomas in the control group. The relative risks in the irradiated group were about 45 for thyroid cancer and 15 for benign thyroid adenomas. The dose-response curve for thyroid cancer was essentially linear, although a linear-quadratic curve could not be ruled out. For thyroid adenomas the risk per rad was somewhat greater at lower doses than at high doses. For both thyroid cancers and adenomas the absolute excess risk per rad was two to three times as great in females as males. Within the limitations imposed by the treatment regimens and the sample size, there was no indication of a 'sparing' effect due to dose fractionation for either thyroid cancers or adenomas. There was an excess risk for both malignant and benign thyroid tumors for at least 40 years post irradiation. For thyroid cancer the radiogenic risk appeared to be additive with respect to time, rather than the age-specific natural rates of cancer being multiplied

Two thousand eight hundred and fifty-six individuals who received X-ray treatments in infancy for an enlarged thymus gland and their 5053 nonirradiated siblings have been followed prospectively since 1953 to evaluate the risk of radiation-induced neoplastic disease. The health status of the entire cohort has been ascertained periodically by mail questionnaire survey. Based on the cumulative experience of five surveys of this cohort, the irradiated group has a statistically significant increased risk for both benign and malignant extrathyroid tumors, the age-adjusted relative risks being 2.0 and 2.2, respectively. Benign tumors of the bone, nervous system, salivary gland, skin, and breast (females only) and malignant tumors of the skin and breast (females only) account for the excess incidence of extrathyroid tumors among the thymic-irradiated individuals. Although a radiation-induced excess of extrathyroid tumors was suggested in an earlier survey of this cohort, small numbers restricted attribution of this excess to specific sites. The implications of these findings are discussed. Thyroid tumors are addressed in a separate paper

A series of about 2200 children who received X-ray treatment for ringworm of the scalp (tinea capitis) during the 1940s and 1950s, and a comparable group of 1400 treated without X ray, have been followed by mail questionnaire for an average of 26 years since treatment to tabulate the incidence of skin cancer. The X-ray treatment consisted of 300-380 R to five overlapping fields on the scalp, to cause complete depilation. This delivered doses of 300-600 rad to various portions of the scalp, with lower doses to the skin of the face and neck. In the irradiated group, 41 persons have had one or more basal cell carcinomas of the scalp or face while only three have been diagnosed in controls. There was a high prevalence of multiple skin cancers in the irradiated group (80 lesions among 41 cases). The minimum latent period for radiation-induced skin cancers was long--about 20 years--and this may be attributable to the young age of the population. The skin cancer risk was particularly pronounced on the face, where there would be more UVR exposure in addition to X-ray exposure. Lightness of complexion proved to be an important factor in the skin cancer risk. In addition, skin cancers were found only among caucasians, even though 25% of the study population were blacks. These findings suggest that UVR exposure levels or sensitivity to such exposure interact with ionizing radiation exposure in defining skin cancer risk.

A number of factors have to be considered in defining the cancer risk from ionizing radiation. These include the radiation sensitivity of the target tissue(s), the temporal pattern of risk, the shape of the dose-incidence curve, the effects of low dose rates, host susceptibility factors, and synergism with other environmental exposures. For the population as a whole the largest sources of radiation exposure are natural background radiation and medical/dental radiation. Radiation exposures in the medical field make up the largest volume of occupational exposures as well. Although new technologies offer opportunities to lower exposures, worker training, careful exposure monitoring with remedial feedback, and monitoring to prevent unnecessary radiodiagnostic procedures may be even more important means of reducing radiation exposure. Screening of irradiated populations can serve a useful preventive function, but only for those who have received very high doses

A computerized, nonsurgical, pulmonary function measurement method was tested for sensitivity and utility in detecting the development of fibrosis. Bleomycin, a fibrogenic agent, was intratracheally instilled into male Fisher 344 rats. Respiratory function was monitored in restrained, awake animals before treatment and for the subsequent 4 wk. In the first week, among responders, a significant (p less than 0.05) drop in body weight, tidal volume, and compliance was accompanied by a significant increase in respiratory frequency. Minute volume increased in the second week. Although body weight, tidal volume, and compliance returned to baseline values in the following weeks, respiratory frequency and minute volume remained significantly elevated. With the methods used here, respiratory rate change was the parameter most sensitive to the effects of bleomycin in vivo

The comparability between an analysis of variance that employs untransformed proportions and one that employs two common arcsine transforms is assessed by using preweaning mouse litter survival data from a toxicological experiment that involves stable laboratory populations. The importance of controlling for litter order, litter size and birth cohort is demonstrated. An adaptation of a nonparametric method suggested by Mantel (1963, Journal of the American Statistical Association 58, 690-700) is proposed as an alternative procedure. Although the results indicate that the nonparametric method is modestly less powerful than the parametric approach, its use is recommended when the assumptions underlying the analysis of variance are questionable. A method for plotting the temporal pattern of the effect of continuous exposure to the toxicant (DDT) on preweaning survival is also presented.