G2 checkpoint control and G2 chromosomal radiosensitivity in cancer survivors and their families.
Significant inter-individual variation in G(2) chromosomal radiosensitivity, measured as radiation-induced chromatid-type aberrations in the subsequent metaphase, has been reported in peripheral blood lymphocytes of both healthy individuals and a range of cancer patients. One possible explanation for this variation is that it is driven, at least in part, by the efficiency of G(2)-M checkpoint control. The hypothesis tested in the current analysis is that increased G(2) chromosomal radiosensitivity is facilitated by a less efficient G(2)-M checkpoint. The study groups comprised 23 childhood and adolescent cancer survivors, their 23 partners and 38 of their offspring (Group 1) and 29 childhood and young adult cancer survivors (Group 2). Following exposure to 0.5 Gy of 300 kV X-rays, lymphocyte cultures were assessed for both G(2) checkpoint delay and G(2) chromosomal radiosensitivity. In Group 1, the extent of G(2) checkpoint delay was measured by mitotic inhibition. No statistically significant differences in G(2) checkpoint delay were observed between the cancer survivors (P = 0.660) or offspring (P = 0.171) and the partner control group nor was there any significant relationship between G(2) checkpoint delay and G(2) chromosomal radiosensitivity in the cancer survivors (P = 0.751), the partners (P = 0.634), the offspring (P = 0.824) or Group 1 taken as a whole (P = 0.379). For Group 2, G(2) checkpoint delay was assessed with an assay utilising premature chromosome condensation to distinguish cell cycle stage. No significant relationship between G(2) checkpoint delay and G(2) chromosomal radiosensitivity was found (P = 0.284). Thus, this study does not support a relationship between G(2)-M checkpoint efficiency and variation in G(2) chromosomal radiosensitivity.
Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria, CA24 3LN, UK. kevin.cadwell@btopenworld.com
Kevin K
KK
Cadwell
Gillian B
GB
Curwen
E Janet
EJ
Tawn
Jeanette F
JF
Winther
John D
JD
Boice
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002875:Chromosomes / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D016195:G2 Phase / Q000235:genetics* / Q000528:radiation effects*; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000528:radiation effects*; D008297:Male; D008938:Mitosis / Q000528:radiation effects; D009369:Neoplasms / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D017741:Survivors