Disease relevance of N-(2-chloroethyl)-N'-(6-chloro-2-methoxy-acridin-9-yl)-N-ethyl-propane-1,3-diamine

• The selective metabolic deactivation of ICR compounds may be related to the findings of previous carcinogenicity studies (1-3) which showed the induction of lung adenomas following i.v. but not i.p. administration of ICR 170 [1].
• Preparations of Chinese hamster ovary (CHO) cells decreased the genotoxicity of 3 ICR compounds (ICR 191, ICR 191-OH and ICR 170-OH), while they did not affect the genotoxicity of ICR 170 in the Salmonella reversion test nor in a DNA-repair test in E. coli [2].
• In xeroderma pigmentosum (XP) C cells there was less repair after UV plus ICR-170 than after each treatment separately; whereas there was an additive effect after UV plus 4NQO and no inhibition of loss of endonuclease sensitive sites [3].
• Aberration analysis revealed that both the mouse lymphoma and CHO cells responded to the clastogenicity of the compounds (except for ICR 170 which was not positive in CHO cells) and that neither cell line was clearly more sensitive than the other to the clastogens tested [4].
• Of several chemicals tested on the elimination of plasmids from Escherichia coli K-12, the compound designated ICR-170 was most effective, applied at 100 mu g/ml, the effect being comparable to that of acriflavin [5].

High impact information on N-(2-chloroethyl)-N'-(6-chloro-2-methoxy-acridin-9-yl)-N-ethyl-propane-1,3-diamine

• Highly mutable sites for ICR-170-induced frameshift mutations are associated with potential DNA hairpin structures: studies with SUP4 and other Saccharomyces cerevisiae genes [6].
• Genetic fine structure analysis and representative DNA sequence determination of ICR-170-induced mutations revealed that there is also a single highly mutable site in SUP4-o and that the mutation is a G . C base-pair insertion at a monotonous run of G . C base pairs [6].
• Based on these results and recent information regarding novel DNA structural conformations, we present a mechanism for ICR-170-induced mutagenesis [6].
• Fifteen independent ICR-170-induced his4 mutations in Saccharomyces cerevisiae were examined by DNA sequence analysis [7].
• Suppressible and nonsuppressible +1 G-C base pair insertions induced by ICR-170 at the his4 locus in Saccharomyces cerevisiae [7].

Biological context of N-(2-chloroethyl)-N'-(6-chloro-2-methoxy-acridin-9-yl)-N-ethyl-propane-1,3-diamine

• The overall data base demonstrates that ICR-170-induced ad-3 mutations result exclusively from gene/point mutations at the ad-3A and ad-3B loci and not multilocus deletion mutations [8].
• Comparison of the dose-response curves for the major classes and subclasses of ICR-170-induced ad-3 mutations demonstrates that the gene/point ad-3 mutations and multiple-locus ad-3 mutations with a separate site of recessive lethal damage elsewhere in the genome have different induction kinetics.(ABSTRACT TRUNCATED AT 400 WORDS)[8]
• ICR-170 was found to increase the reversion frequency by ten- to 15-fold at its LD50, although most of the frameshifts that it induced were single-base insertions outside the microsatellite sequence [9].

Anatomical context of N-(2-chloroethyl)-N'-(6-chloro-2-methoxy-acridin-9-yl)-N-ethyl-propane-1,3-diamine

• The results indicate that in normal human fibroblasts there are different rate limiting steps for removal of chemical and physical damages from DNA and that XP cells have a different repair system for ICR-170, not just a lower level, than normal cells [3].
• Despite the fact that ICR-170 induces little DNA repair in xeroderma pigmentosum (XP) cells, which are deficient in excision repair, the inhibition of DNA synthesis induced by this agent was less in XP cells than in HeLa cells [10].

Associations of N-(2-chloroethyl)-N'-(6-chloro-2-methoxy-acridin-9-yl)-N-ethyl-propane-1,3-diamine with other chemical compounds

• The data provide further evidence that ICR-191 and ICR-170 cause structural gene mutations in mammalian cells and also suggest that ICR-191, ICR-170, and N-ethyl-N-nitrosourea induce similar types of mutations in Chinese hamster ovary cells [11].
• The nature of the N2 effect for ICR-170, i.e., the greater mutagenic and lethal activities of this agent in the presence of N2 than O2, has been studied at the ad-3 region of Neurospora crassa [12].
• Induction of mutations in the aza-3 gene was detected after treatment of conidia with ultraviolet light, X-rays, ethyl methanesulfonate (EMS), or the acridine mustard, ICR-170 [13].
• 6-Thioguanine-resistant mutants were induced in V79 Chinese hamster cells with 2-aminopurine, ICR-170 and hycanthone [14].

Gene context of N-(2-chloroethyl)-N'-(6-chloro-2-methoxy-acridin-9-yl)-N-ethyl-propane-1,3-diamine

• ICR-170-induced mutations in the CYC1 gene of the yeast Saccharomyces cerevisiae were investigated by genetic and DNA sequence analyses [15].
• Combined with previous DNA sequence data, 21 ICR-170-induced his4 mutations distributed at 16 different sites were analyzed [7].

References