methylnitronitrosoguanidine and 2-vanillin

The enhancing effect of o-vanillin (2-hydroxy-3-methoxybenz-aldehyde) on mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was characterized with mutational specificity. The mutational spectrum of MNNG-induced mutations in the presence of o-vanillin was compared with that in the absence of o-vanillin by means of a series of mutant lacZ genes in E. coli that can detect each of the six types of base substitutions and five kinds of frameshift events. In the absence of o-vanillin, the mutational spectrum induced by MNNG consisted mainly of G.C-->A.T transitions and, to a lesser extent, -1(G.C) frameshift mutations. By adding o-vanillin at 75 micrograms/plate, a marked enhancement was observed in two transitions, G.C-->A.T and A.T-->G.C, and in two frameshift mutations, +1(G.C) and -1(G.C). Only a small change was observed in the -2(C.G-G.C) fraction. Regarding the MNNG-induced frameshifts at the A.T base pair, the +1(A.T) frameshift was much more enhanced by o-vanillin than the -1(A.T) frameshift.

Topics: Benzaldehydes; beta-Galactosidase; Dose-Response Relationship, Drug; Drug Synergism; Escherichia coli; Frameshift Mutation; Genes, Bacterial; Methylnitronitrosoguanidine; Mutagenicity Tests; Mutagens; Point Mutation

Mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were strongly enhanced in the presence of o-vanillin in E. coli B. The enhancement was also observed in uvrA, umuC, recA, polA, or alkB mutants. This effect was lower in an alkA mutant, but was restored in an alkA umuC double mutant. By contrast, the enhancing effect was almost blocked in an ada and ada umuC double mutant. It was necessary to add simultaneously MNNG and o-vanillin to the growth medium. Further investigations were conducted on the induction of ada and umuC genes using ada'-lacZ' and umuC'-lacZ' plasmids. o-Vanillin suppressed the induction of the ada gene by MNNG treatment, but not that of the umuC gene. In fact expression of the umuC gene was induced by lower concentrations of MNNG in the presence of o-vanillin. The results suggest that o-vanillin inhibits induction of the adaptive response, and consequently, the MNNG-induced mutation frequency is increased due to unrepaired O6-methylguanine.

Topics: Benzaldehydes; beta-Galactosidase; DNA Repair; DNA, Bacterial; Escherichia coli; Methylnitronitrosoguanidine; Mutation

2-Hydroxy-3-methoxybenzaldehyde (omicron-vanillin), the antimutagenic effect of which has been reported on mutagenesis induced by 4-nitroquinoline 1-oxide (4NQO) in Escherichia coli WP2s, enhanced N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced mutagenesis in the same strain. A remarkable enhancement of mutagenesis provoked by N-methyl-N-nitrosourea (MNU) was also observed by the addition of omicron-vanillin. No enhancing effect was observed on mutagenesis induced by other mutagens such as methyl methanesulfonate (MMS), dimethylsulfate, N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), N-ethyl-N-nitrosourea (ENU), ethyl methanesulfonate, diethylsulfate, 4NQO and furylfuramide (AF-2). On the contrary, omicron-vanillin greatly suppressed AF-2- and 4NQO-induced mutagenesis and showed a slight suppressing effect against mutagenesis induced by MMS, ENNG and ENU. One possible explanation for the enhancing effect of omicron-vanillin on the mutagenesis induced by MNNG or MNU in E. coli WP2s may be inhibition of an inducible adaptive response. Among 7 derivatives of omicron-vanillin, 2-hydroxy-3-ethoxy-benzaldehyde, omicron-hydroxybenzaldehyde and m-methoxybenzaldehyde showed an enhancing effect on MNNG-induced mutagenesis.

Topics: Benzaldehydes; Escherichia coli; Methylnitronitrosoguanidine; Mutagens; Mutation; Structure-Activity Relationship