From: Evidence That BRCA1- or BRCA2-Associated Cancers Are Not Inevitable
System and reference | Assay | Spontaneous SCE frequency | Test mutagen | SCE (max)/cell with mutagen | Independent supporting data |
---|---|---|---|---|---|
CHO cells in culture (54) | BrdU extrapolated to low doses | 1.32/cell/cell cycle | Â | Â | Lower SCE frequency in vivo |
Bovine autosomes 16 and 26 and Y chromosomes (55) | BrdU for one replication then CO-FISH | 3.7/metaphase | Â | Â | Â |
Ear fibroblasts from FYDR mice (20) | Fluorescent phenotype generated by homologous recombination event on chromosome 1 | 1.2–1.4 recombinants per million cell divisions | MMC | ~150 recombinant cells/million cell divisions |  |
FYDR mice carrying a transgene; spontaneous HR in pancreas that contains few S phase cells (23) | Fluorescent phenotype representing homologous recombination event | 2.5 recombinant cells/million cell divisions; some mice have zero recombinants; ~10/million cells in pancreas of individual animals (range ~0–300) | MMC | ~90–135 per million cell divisions | p53status does not affect spontaneous SCE frequency |
Intact mouse embryo (21) | Expression of acetylcholine receptor due to recombination | 1–2 × 10−6/cell division |  |  | Frequency of recombination in intact embryo is similar to that in cultured cells |
Human fibroblasts from a Lesch-Nyhan donor (56) | Growth in HAT medium due to recombination at HPRT locus | 10–30 × 10−6 per cell per generation | Methyl nitrosoguanidine, UV, chromium oxide, MMC, DES, nickel chloride, sodium azide | Dose-dependent 2.4 -to 10-fold increase | Noncarcinogens showed much less activity Dose-dependent induction of HAT reversion is concordant with in vivo carcinogenesis |