Lymphoblastoid cell lines (LCLs) established from
chromosomal breakage syndromes or related
genetic disorders have been used to study the effects of
mutagens on human lymphoid cells. The disorders studied include
xeroderma pigmentosum,
ataxia telangiectasia,
Fanconi's anemia,
Bloom's syndrome and Cockayne's syndrome. Three approaches were used to assess the cells' ability to cope with a particular
mutagen: (1) assaying recovery of
DNA synthetic capabilities as measured by [3H]
thymidine (dT) incorporation; (2) measurements of classical excision DNA repair by isopyknic sedimentation of
DNA density labeled with 5-bromo-2-deoxyuridine (
BrdU); (3) determining cell survival by colony formation in microtiter plates. LCLs established from
xeroderma pigmentosum showed increased sensitivities to ultraviolet (354 nm) light and
N-acetoxy-2-acetylaminofluorene (AAAF) as determined by
DNA synthesis or colony formation and had diminished levels of excision-repair. Cockayne's syndrome LCLs, on the other hand, had increased sensitivities to ultraviolet (UV) light, AAAF and
N-methyl-N'-nitro-N-nitrosoguanidine (
MNNG) while showing near normal levels of DNA-repair
after treatment with each agent. An LCL established from
ataxia telangiectasia had decreased DNA repair synthesis and defective colony-forming ability following treatment with
MNNG. LCLs, in addition to ease of establishment, appear likely to provide useful material for the study of DNA repair replication and its relationship to
carcinogenesis.