Lower rates of thymidine incorporation into DNA of skin fibroblasts from patients with adenomatosis of the colon and rectum.
Thymidine incorporation into DNA was examined in confluent fibroblast cultures which had been further arrested by 7-9 days' growth on 0.5% serum-supplemented medium. There were 13 fibroblast lines from patients with adenomatosis of the colon and rectum (ACR) and seven control fibroblast strains from unaffected relatives and spouses of ACR patients. After 24 h an ACR fibroblast strain showed a decreased rate of unscheduled DNA synthesis (UDS), whereas no such effects were observed with the control fibroblast strain. It was shown that the difference in UDS rates between control and ACR fibroblast strains was not due to [3H]-dThd catabolism and/or disappearance in the culture medium after a 34-h labelling period. When the percent increases in N-acetoxy-2-acetylaminofluorene (NA-AAF)-induced UDS and in [3H]-dThd incorporation in the presence of 10 mM hydroxyurea were compared between 24 h and 34 h incubation, the 13 ACR fibroblast lines were significantly lower compared to the corresponding values calculated for the seven control fibroblast strains. The ACR fibroblasts also had significantly elevated levels of spontaneous chromosome aberrations compared to controls. Furthermore, the percent increase in NA-AAF-induced UDS was negatively correlated with the level of spontaneous chromosome aberrations. These data suggest that there is a genetic instability in the cells from ACR patients that can be estimated by both UDS and cytogenetic analyses.
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D000099:Acetoxyacetylaminofluorene / Q000494:pharmacology; D000328:Adult; D002648:Child; D003110:Colonic Neoplasms / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009377:Multiple Endocrine Neoplasia / Q000378:metabolism*; D012004:Rectal Neoplasms / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism*
D000099:Acetoxyacetylaminofluorene; D004247:DNA; D013936:Thymidine