Chromosomal abnormalities in skin following total body or total lymphoid irradiation

Abstract

Patients undergoing bone marrow transplantation often receive total body or total lymphoid irradiation as part of the conditioning regimen prior to marrow infusion. The cytogenetic effects of this therapy on skin fibroblasts were studied. Fibroblast cultures from eight skin biopsies were harvested in early passages for G-banded chromosome analysis. Four biopsies were from three patients who had high-dose cyclophosphamide and total body radiotherapy; one was from within and one was from outside the radiation field of a patient who had high-dose cyclophosphamide and lymphoid radiotherapy, one was from a patient who had combination chemotherapy alone, and one was from a normal control. No abnormal mitoses were found in the control or the patient who had chemotherapy alone, and only two of 30 mitoses from skin outside the lymphoid radiotherapy field were abnormal. However, most cells (49-88%) from five biopsies within radiotherapy fields were abnormal. Typically, abnormal karyotypes were pseudodiploid and contained multiple balanced rearrangements, of which reciprocal translocations were most common. The data indicate that the radiotherapy used for bone marrow transplantation induces extensive, sustained chromosome abnormalities in vivo in skin fibroblasts.

Frequent induction of chromosomal aberrations in in vivo skin fibroblasts after allogeneic stem cell transplantation: hints to chromosomal instability after irradiation

“…It is unlikely, that all these aberrations developed ex vivo in culture, because most skin metaphases were normal before SCT. In the literature there is only one small series of four pediatric patients after TBI or total lymphoid irradiation, where authors found 49 to 88 % aberrant metaphases in the skin biopsies taken within radiotherapy fields [ 19 ]. A few case reports have also been published describing chromosomal aberrations in skin fibroblasts after in vivo radiation exposure [ 15 – 18 , 25 ], but without comparison to pre-radiation metaphases.…”

“…Therefore it cannot be excluded that the extent of the observed cytogenetic damage in the present study may have been influenced in part by radiation enhancing effects of chemotherapy. However in a small series of SCT-patients, abnormal karyotypes were only observed in those with TBI, but not in those without [ 19 ].…”

“…A stronger hint to in vivo clonality could be found in three of our patients with identical aberrations in cultures from independently set up pieces of the same biopsy. Hints to in vivo clone formation come from case reports by others as well [ 15 , 17 – 19 ]. The strongest evidence for in vivo clone formation was reported by Mouthuy and Dutrillaux, who found cells with identical aberrations in two skin biopsies, which were taken with a time interval of one year [ 15 ].…”

“…Chromosomal aberrations have been described in cultured skin fibroblasts after accidental irradiation in single patients [ 15 , 16 ] and in a few patients having received radiotherapy [ 17 – 19 ]. No systemic in vivo cytogenetic analysis of irradiated skin fibroblasts has been performed in patients.…”