Rd. Gill et al., MUTAGENIC SPECIFICITY OF THE (-DIOL EPOXIDE OF DIBENZ[A,J]ANTHRACENE IN THE SUPF GENE OF AN ESCHERICHIA-COLI PLASMID()ANTI), Molecular carcinogenesis, 8(3), 1993, pp. 145-154
This study was designed to examine the mutagenic specificity of (+)ant
i-dibenz[a,j]anthracene 3,4-diol-1,2-epoxide ((+)anti-DB[a,j]A-DE) in
SOS-induced repair-proficient Escherichia coli ES87 (DELTApro-lac, str
A)/F'(pro+, lacl(Q), lacl(am26), lacZDELTAM15). The plasmid pUB3, whic
h contains the mutation target gene, supF, was modified with (+)anti-D
B[a,j]A-DE in vitro (two to five adducts/plasmid) and then transformed
into bacteria by electroporation. The spontaneous mutation frequency
for unmodified pUB3 in uninduced cells was about 2 X 10(-6) and for SO
S-induced cells, about 8 x 10(-6) . The spontaneous supF- mutations we
re primarily insertions, deletions, and frameshifts. The mutation freq
uency for (+) anti-DB[a,j]A-DE-modified pUB3 was about 8 x 10(-6) and
about 32 x 10(-6) for uninduced cells and SOS-induced cells, respectiv
ely. (+)anti-DB[a,j]A-DE induced primarily point mutations in supF in
SOS-induced cells. GC-AT transitions were the major mutations observed
in SOS-induced cells (37%). GC-->TA (21%) and GC-->CG (8.6%) transver
sion mutations were also observed, whereas mutations at AT base pairs
were rare (1.9%). Furthermore, a large number of tandem GC/GC-AT/AT tr
ansition mutations were also observed (about 15% of all mutations in S
OS-induced cells). Taken together, single and tandem GC-->AT mutations
accounted for slightly over half (about 51%) of the mutations observe
d in SOS-induced cells. These results demonstrated that (+)anti-DB[a,j
]A-DE was mutagenic in repair-proficient E. coli, however, unlike othe
r polycyclic aromatic hydrocarbons that induce primarily transversion
mutations, (+)anti-DB[a,j]A-DE caused mostly GC-->AT transitions. (C)
1993 Wiley-Liss, Inc.