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Table 2 Spontaneous SCEs measured in different systems or by different methods differ greatly from SCEs measured in human lymphocytes.

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

  

Lower SCE frequency in vivo

Bovine autosomes 16 and 26 and Y chromosomes (55)

BrdU for one replication then CO-FISH

3.7/metaphase

   

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

  1. CHO, Chinese hamster ovary; CO-FISH, chromosome orientation fluorescence in situ hybridization; FYDR, fluorescent yellow direct repeat; HR, homologous recombination; HAT, hypoxanthine, amethopterin (methotrexate) and thymidine; UV, ultraviolet irradiation; HPRT, hypoxanthine-guanine phosphoribosyltransferase; DES, diethylstilbestrol.