Factors Affecting and Significance of G₂Chromatin Radiosensitivity in Predisposition to Cancer

Abstract

The frequencies of chromatid breaks and gaps in metaphase cells fixed 2 h after G2 phase X-irradiation (1 Gy) were in almost all cases at least two- to three-fold higher in skin fibroblasts from individuals with genetic conditions predisposing to cancer than in comparable cells from clinically normal controls. Previously, we reported this response in all cancer-prone genetic disorders tested including ataxia telangiectasia, Bloom's syndrome, Fanconi's anemia, xeroderma pigmentosum (XP), familial polyposis, Gardner's syndrome, hereditary malignant melanoma, dysplastic nevus syndrome and cancer family members. One exception was XP-A. In this report we add information on skin fibroblasts from retinoblastoma, Wilms' tumor and XP-C patients, 13 clinically normal controls and six cell lines from fetal or infant cells. Factors affecting the response are identified and include pH, temperature, cell density, culture medium or serum, microbial contamination and visible light exposure (effective wavelength 405 nm). Because of experimental variability, known normal controls should be used in each group of assays. With adequate control of the above factors this response could provide the basis of a test for detecting individuals carrying genes that predispose to a high risk of cancer.

Chromosomal radiosensitivity as a marker of predisposition to common cancers?

“…The majority of aberrations were chromatid breaks and gaps that were greater than the width of the chromatid. Smaller achromatic lesions (gaps) were ignored (Sanford et al, 1989).…”

Chromosomal radiosensitivity in breast cancer patients with a known or putative genetic predisposition

“…In a large number of patients with inherited cancer-prone disorders such as ataxia-telangiectasia, Nijmegen breakage syndrome and hereditary retinoblastoma an enhanced chromosomal radiosensitivity has been demonstrated (Sanford et al, 1989;reviewed in Scott et al, 1999). More recently elevated chromosomal radiosensitivity has also been observed in significant proportions of patients with sporadic cancers with no obvious family history (Scott et al, 1994;Terzoudi et al, 2000).…”

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G2chromosomal radiosensitivity

“…Unrepaired damage is seen at the subsequent metaphase as chromatid gaps and breaks. The assay was originally developed in fibroblasts as a possible measure of cancer predisposition [Parshad et al, 1983;Sanford et al, 1989] and subsequently adapted for lymphocytes [Scott et al, 1996]. Enhanced G 2 chromosomal radiosensitivity has been detected in several welldefined cancer susceptibility syndromes, most notably ataxia telangiectasia [Parshad and Sanford, 2001].…”