Variation in the expression of aphidicolin-induced fragile sites in human lymphocyte cultures

Abstract

A correlation between specific fragile sites and cancer breakpoints has been suggested raising the question of fragile site expression as a predisposing factor in the occurrence of cancer in some persons. Before addressing the question of increased fragility among patients at high risk for cancer, we analyzed the variability of aphidicolin-induced fragile sites among nine normal persons and also among repeated samples from three of these individuals. Considerable variation in both the frequency and location of these fragile sites was observed and the data strongly suggest the significant variation of 6 of the 16 selected sites to be primarily due to sampling differences. These findings indicate that the use of fragile sites as a screening tool for patients at high risk of cancer should be carefully monitored relative to the variation inherent in both culture and individual expression.

A population cytogenetic study of a common fragile site, fra(3)(p14), in a healthy population

“…It is presently not conclusive whether any common fragile sites are expressed comparably with each other. Previous studies (Craig-Holmes et aL, 1987;Rao etal., 1988a, b;Fuster et al, 1989) sometimes exhibited individuals whose lymphocytes express other common fragile sites more frequently than fra(3)(pl4). Thus for the moment the findings obtained presently should be confined to be true for fra(3)(pl4).…”

“…Regarding this question, Craig-Holmes et aL (1987) observed that expression of common fragile sites by APC treatment was incompatible among three consecutive samplings from the same three persons. Smeets et aL (1986) also demonstrated that the expression of fra(3)(pl4) with the folate deficient condition was significantly disagreed between two consecutive samples in three of the six cases.…”

Common fragile sites induced by folate deprivation, BrdU and aphidicolin: Their frequency and distribution in Japanese individuals

“…(1985); 8, Craig-Holmes et al (1987);9, Marlhens et aL (1986);10, Rao et al (1988). individuals in our study.…”

“…Of the latter five, those at 4q34 and 6@2, both BrdU induced, were each found in only one individual, and thus need further confirmation. The site at 3q26.2, both folate sensitive and BrdU induced, has not been described, but a site at the adjoining band 3q27 has been reported (Glover, 1984;Yunis and Soreng, 1984;Craig-Holmes et al, 1987). The question of whether or not they are identical remains to be answered.…”

“…Reports on c-fra sites in Caucasians have included those induced by folic acid deprivation (Sutherland, 1979;Yunis and Soreng, 1984;Marlhens et al, 1986), by treatment with methotrexate (Barbi et al, 1984), fluorodeoxyuridine (Barbi et al, 1984;Daniel et aL, 1984;Yunis and Soreng, 1984;Rao et al, 1988), 5-bromodeoxyuridine , 5-azacytidine , caffeine (Yunis and Soreng, 1984), or aphidicolin (Glover, 1984;Craig-Holmes et al, 1987;Rao et aL, 1988). Little has been known of their individual or racial difference.…”