Sensitivity of cultured cells to gamma radiation in a patient exhibiting marked in vivo radiation sensitivity.

An apparently normal 13-year-old girl developed multiple severe complications over several years after radiation therapy for Stage IIB Hodgkin's disease, including hypothyroidism, esophageal stenosis, restrictive lung and pericardial disease, extrahepatic biliary fibrosis, and sudden death presumed secondary to a myocardial infarction. Cultured skin fibroblast cells from the patient exhibited marked sensitivity to gamma radiation in vitro. The D0 of the radiation survival curve (the inverse of the straight line portion of the curve and that dose of radiation which theoretically leads to one lethal hit per cell) was 89 cGy, compared to a mean D0 for nine normal individuals of 155 cGy, and 85 cGy for two patients with the radiation sensitive disease ataxia-telangiectasia (AT). Profound clinical heterogeneity in response to cancer therapeutic agents may exist, with some individuals who show no signs or symptoms of DNA repair deficiency (for example, as is manifested by individuals with AT) exhibiting marked in vivo and in vitro sensitivity to certain DNA-damaging agents.