Multiplicity reactivation and mutagenesis of trimethylpsoralen-damaged herpes virus in normal and Fanconi's anaemia cells.
Fanconi's anaemia (FA) cells are hypersensitive to the lethal effect of DNA cross-linking compounds. Herpes simplex virus (HSV) has been used here as a probe to monitor in FA cells repair of psoralen damage of which cross-links are a part. The replication of HSV is impaired when its DNA contains covalently photobound psoralen molecules. In comparison to other psoralens, 4,5',8-trimethylpsoralen (4,5',8-TMP) is one of the most photoreactive psoralens and it forms a relatively high proportion of DNA interstrand cross-links. TMP-damaged HSV is efficiently reactivated by multiple infection in human fibroblasts. The extent of multiplicity reactivation is greater in cells from FA donors (five strains tested) than in normal cells (three strains). Mutagenesis studied in the viral thymidine kinase locus revealed that: (i) spontaneous viral mutation rate is lower in FA than in normal cells; and (ii) under conditions of multiple infection, the mutation rate is either greater (normal cells) or unchanged (FA cells) in the progeny from psoralen-damaged HSV compared to that from untreated virus. Taken together, these observations suggest that the pathway underlying multiplicity reactivation of psoralen-damaged HSV is error-free in FA cells relative to normal cells.
Coppey
J
J
Institut Curie-Biologie, Paris, France.
Sala-Trepat
M
M
Lopez
B
B
D000328:Adult; D000741:Anemia, Aplastic / Q000382:microbiology*; D002648:Child; D004305:Dose-Response Relationship, Drug; D005199:Fanconi Anemia / Q000382:microbiology*; D005347:Fibroblasts / Q000032:analysis / Q000382:microbiology; D011564:Furocoumarins / Q000633:toxicity*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009152:Mutagenicity Tests; D009154:Mutation; D018139:Simplexvirus / Q000187:drug effects / Q000254:growth & development*; D012867:Skin / Q000166:cytology; D014307:Trioxsalen / Q000008:administration & dosage / Q000633:toxicity*; D010948:Viral Plaque Assay; D014775:Virus Activation / Q000187:drug effects
D011564:Furocoumarins; D014307:Trioxsalen