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Unexpected sensitivity to radiation of fibroblasts from unaffected parents of children with hereditary retinoblastoma
Author(s) -
Fitzek Markus M.,
Dahlberg William K.,
Nagasawa Hatsumi,
Mukai Shizuo,
Munzenrider John E.,
Little John B.
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10401
Subject(s) - retinoblastoma , proband , locus (genetics) , genetics , biology , ploidy , clonogenic assay , mutation , gene , cell
The response to ionizing radiation was examined in diploid skin fibroblasts derived from 5 patients with hereditary type retinoblastoma as well as their parents. Unexpected sensitivity to cell killing, as measured by clonogenic survival, as well as enhanced radiation‐induced G 1 arrest were observed in at least 1 parental fibroblast strain in all 5 families. In all cases, parental strains were equally or more radiosensitive than the probands. The mutation of the retinoblastoma gene (RB) determined in 4 of 5 probands was either absent from the parental cells, as expected from the negative family histories, or identical, in 1 father who was a known carrier. In the fifth family, the family history was negative for retinoblastoma. We hypothesize that the increased parental cell sensitivity to radiation suggests the presence of an as yet unrecognized genetic event occurring in 1 or both parents of children with retinoblastoma. Whether it increases mutability of the RB locus or other loci or interacts with RB is conjectural. © 2002 Wiley‐Liss, Inc.