Comparison of the types of mutations induced by 7,12-dimethylbenz[a]anthracene in the lacI and hprt genes of Big Blue rats.
An important question regarding the use of transgenic reporter genes to detect mutation in rodents is how the types of mutations recovered in transgenes compare with the types of mutations found in endogenous genes. In this study, we examined mutations induced by 7,12-dimethylbenz[a]anthracene in the lacI transgene and the endogenous hprt gene of lymphocytes from Big Blue rats and in the hprt gene of lymphocytes from nontransgenic Fischer 344 rats. The overall mutation profiles found in these genes were remarkably similar: the majority of mutations were base pair substitutions, with the most common mutation being A:T-->T:A transversion. Differences were found for the mutational profiles in the endogenous gene and transgene with respect to the location of the mutations and the orientation of basepair substitutions in the DNA strands. In most cases, these differences could be explained by the nature of the target genes. The results support the use of the lacI transgene for detecting in vivo mutation.
Mittelstaedt
R A
RA
rmittelst@nctr.fda.gov
Manjanatha
M G
MG
Shelton
S D
SD
Lyn-Cook
L E
LE
Chen
J B
JB
Aidoo
A
A
Casciano
D A
DA
Heflich
R H
RH
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D030801:Animals, Genetically Modified; D001426:Bacterial Proteins / Q000187:drug effects* / Q000235:genetics*; D002273:Carcinogens / Q000494:pharmacology* / Q000633:toxicity; D004252:DNA Mutational Analysis; D029968:Escherichia coli Proteins; D007041:Hypoxanthine Phosphoribosyltransferase / Q000187:drug effects* / Q000235:genetics*; D056968:Lac Repressors; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D017354:Point Mutation / Q000187:drug effects / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D012097:Repressor Proteins / Q000187:drug effects* / Q000235:genetics*; D019076:Transgenes / Q000187:drug effects / Q000235:genetics
D001426:Bacterial Proteins; D002273:Carcinogens; D029968:Escherichia coli Proteins; D056968:Lac Repressors; D012097:Repressor Proteins; D015127:9,10-Dimethyl-1,2-benzanthracene; D007041:Hypoxanthine Phosphoribosyltransferase