Inactivation by nitrogen mustard of plasmids introduced into normal and Fanconi's anaemia cells.
An SV40-transformed Fanconi's anaemia (FA) cell line, GM6914, exhibits approximately 2.4-fold increased sensitivity to the cytotoxic effects of nitrogen mustard (NM) when compared with the normal line, MRC5-V1. Host cell reactivation of NM-treated plasmid has been investigated using transient expression vectors which contain the chloramphenicol acetyltransferase (CAT) gene. In both cell types there is a similar, dose-dependent reduction in CAT expression which correlates with an increase in NM-induced DNA-interstrand crosslinking. The data are consistent with two possible mechanisms for inactivation of the plasmid. Either a single crosslink anywhere within the plasmid is sufficient to prevent transcription of the cat gene. Alternatively, inactivation may result from some other more prevalent NM-induced lesions within the cat coding sequence.
Dean
S W
SW
MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton, Great Britain.
Sykes
H R
HR
Lehmann
A R
AR
D000123:Acetyltransferases / Q000235:genetics; D000741:Anemia, Aplastic / Q000235:genetics*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D015500:Chloramphenicol O-Acetyltransferase; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004260:DNA Repair; D005199:Fanconi Anemia / Q000235:genetics*; D006801:Humans; D008466:Mechlorethamine / Q000494:pharmacology*; D010957:Plasmids / Q000187:drug effects; D014162:Transfection
D003432:Cross-Linking Reagents; D008466:Mechlorethamine; D000123:Acetyltransferases; D015500:Chloramphenicol O-Acetyltransferase