COMPARISON OF THE MUTAGENICITY AND MUTAGEN SPECIFICITY OF ETHYLENIMINE WITH TRIETHYLENEMELAMINE IN THE AD-3 REGION OF HETEROKARYON-12 OF NEUROSPORA-CRASSA
Fj. Deserres et al., COMPARISON OF THE MUTAGENICITY AND MUTAGEN SPECIFICITY OF ETHYLENIMINE WITH TRIETHYLENEMELAMINE IN THE AD-3 REGION OF HETEROKARYON-12 OF NEUROSPORA-CRASSA, Mutation research, 328(2), 1995, pp. 193-205
Studies have been performed to compare the mutagenicity and mutagenic
specificity of the trifunctional alkylating agent, triethylenemelamine
(TEM), and a closely related monofunctional agent, ethylenimine (EI),
in the adenine-3 (ad-3) region of a 2-component heterokaryon (H-12) o
f Neurospora crassa. The primary objective of our studies was to chara
cterize the genetic damage produced by each agent with regard to (1) m
utagenic potency, and (2) the spectrum of specific-locus mutations ind
uced in a lower eukaryotic organism. As in higher eukaryotes, specific
-locus mutations in the ad-3 region of H-12 result from gene/point mut
ations, multilocus deletion mutations, and multiple-locus mutations. S
pecific-locus mutations resulting from gene/point mutation and multilo
cus deletion mutation can be detected in higher eukaryotes, but multip
le-locus mutations can be detected only with difficultly or not at all
. Our experiments with the ad-3 forward-mutation assay have demonstrat
ed that TEM is a strong mutagen (maximum forward-mutation frequency be
tween 100 and 1000 ad-3 mutations per 10(6) survivors) and EI is a mod
erate mutagen (maximum forward-mutation frequency between 10 and 100 a
d-3 mutations per 10(6) survivors) for the induction of specific-locus
mutations in the ad-3 region. Classical genetic tests were used to id
entify the different genotypic classes and subclasses among the EI- an
d TEM-induced ad-3 mutations from each experiment. The overall data ba
se demonstrates that both EI- and TEM-induced ad-3 mutations result pr
edominantly from gene/point mutations at the ad-3A and ad-3B loci (97.
3% and 95.5%, respectively), and infrequently from multilocus deletion
mutations (2.7% and 4.5%, respectively). Heterokaryon tests for allel
ic complementation on TEM- and EI-induced ad-3B mutations, however, ha
ve revealed a difference between the percentages showing allelic compl
ementation (63.1% and 40.9%, respectively). Based on the specific reve
rtibility of complementing and noncomplementing ad-3B mutations induce
d by other agents, this difference in the percentages of ad-3B mutatio
ns showing allelic complementation results from a difference between t
he spectrum of genetic alterations at the molecular level. In addition
, comparison of the ratio of TEM-induced ad-3A and ad-3B mutations wit
h those induced by EI has revealed a difference between the ad-3B/ad-3
A ratios. Additional comparisons are made of the