TY - JOUR
T1 - Chromosomal fragility in the cancer-prone disease xeroderma pigmentosum preferentially involves bands relevant for cutaneous carcinogenesis
AU - Lanza, Annalisa
AU - Lagomarsini, Paola
AU - Casati, Alessandra
AU - Ghetti, Pierluigi
AU - Stefanini, Miria
PY - 1997
Y1 - 1997
N2 - Spontaneous and folate-induced chromosomal fragility was analyzed in peripheral blood lymphocytes from 6 patients affected by the cancer-prone disease xeroderma pigmentosum (XP), from the parents of 4 of the patients, and from 12 normal subjects. All XP patients were defective in nucleotide- excision repair; 4 belonged to group C and I each to groups A and D. A tendency toward increased spontaneous chromosomal fragility was observed in the XP family members, and lesions indicating substantial chromosomal damage, which were not observed in any healthy donors, were frequently found. The spontaneous lesion sites in lymphocytes from homozygous and heterozygous carriers of XP defects appeared to be significantly associated with those observed in normal skin fibroblasts from the same subjects. These XP spontaneous fragility sites showed a statistically significant association with the rearrangement breakpoints reported in skin pre-tumoral and tumoral lesions from normal and unrelated XP donors. Under conditions of folate deprivation, the chromosomal fragility level, the pattern and the frequency of expression of fragile sites in XP patients and in their parents were similar to normal. However, XP patients generally showed a higher susceptibility to breakage at sites described as mutagen and carcinogen targets.
AB - Spontaneous and folate-induced chromosomal fragility was analyzed in peripheral blood lymphocytes from 6 patients affected by the cancer-prone disease xeroderma pigmentosum (XP), from the parents of 4 of the patients, and from 12 normal subjects. All XP patients were defective in nucleotide- excision repair; 4 belonged to group C and I each to groups A and D. A tendency toward increased spontaneous chromosomal fragility was observed in the XP family members, and lesions indicating substantial chromosomal damage, which were not observed in any healthy donors, were frequently found. The spontaneous lesion sites in lymphocytes from homozygous and heterozygous carriers of XP defects appeared to be significantly associated with those observed in normal skin fibroblasts from the same subjects. These XP spontaneous fragility sites showed a statistically significant association with the rearrangement breakpoints reported in skin pre-tumoral and tumoral lesions from normal and unrelated XP donors. Under conditions of folate deprivation, the chromosomal fragility level, the pattern and the frequency of expression of fragile sites in XP patients and in their parents were similar to normal. However, XP patients generally showed a higher susceptibility to breakage at sites described as mutagen and carcinogen targets.
UR - http://www.scopus.com/inward/record.url?scp=0031456056&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031456056&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0215(19971219)74:6<654::AID-IJC17>3.0.CO;2-5
DO - 10.1002/(SICI)1097-0215(19971219)74:6<654::AID-IJC17>3.0.CO;2-5
M3 - Article
C2 - 9421365
AN - SCOPUS:0031456056
VL - 74
SP - 654
EP - 663
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 6
ER -