Disease relevance of ICR 191

• Here, by transfecting ICR-191-treated M13 AB28 single-stranded DNA into Escherichia coli, we show that base substitutions are predominantly targeted to guanines [1].
• Mutation induction in Haemophilus influenzae by ICR-191. II. Role of DNA replication and repair [2].
• Quantitative forward-mutation specificity of mono-functional alkylating agents, ICR-191, and aflatoxin B1 in mouse lymphoma cells [3].
• We infer that ICR-191 and AFB1 very rarely cause base substitutions in S49 cells, but that their activities are consistent with production of deletions, insertions or chromosomal aberrations [3].
• Concentration-dependent mutagenicity of ICR-191 has been measured in Salmonella typhimurium strain TA98 and in a diploid human cell line [4].

High impact information on ICR 191

• A series of uniflagellar mutants isolated following mutagenesis of Chlamydomonas reinhardtii (strain 137c) with ICR-191 show a remarkable positional phenotype [5].
• Heteroalleles were generated in the TK+/+ parent B-lymphoblast cell line WIL-2 by repeated exposure to the alkylating nitrogen mustard ICR-191, which preferentially causes +1 or -1 frameshifts [6].
• Nitrosoguanidine, ethyl methanesulfonate, ICR 191, and x-rays were used [7].
• Frame-restoring point mutations, restoration of original sequences, and phenocopy reversion by acquisition of aminopterin resistance were also found among X-ray-induced revertants, whereas the ICR-191-induced revertants examined show only loss of the exon 7 frameshift [8].
• Line 4:2 reverts to TK+ at a lower spontaneous frequency than does 6:86 but can be induced with similar kinetics by ICR-191 [8].

Chemical compound and disease context of ICR 191

• Toward this goal, M13 replicative form DNA was subjected to in vitro adduction with the acridine mutagen ICR-191 and transfected into Escherichia coli [9].

Biological context of ICR 191

• Logarithmically growing suspension cultures of L1210 and P388 cells were treated with ethyl methanesulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, or ICR-191 at concentrations which result in 20 to 30% cell survival [10].
• Eleven variants producing only heavy (H) chains have been isolated from the P3 cell line after mutagenesis with either ICR-191 or nitrosoguanidine [11].
• Genetic and sequence analysis of frameshift mutations induced by ICR-191 [12].
• Conversion to higher ploidy did not occur when diploid cell cultures were exposed to ICR 191 [13].
• The effects of an acridine half-mustard, ICR 191, on the growth rate and ploidy of four haploid and two diploid lines of Rana pipiens cells in culture were studied [13].

Anatomical context of ICR 191

• Despite the greater mutagenic potency in the absence of metabolic systems, ICR 191 was deactivated far more efficiently and rapidly than ICR 170 by a variety of mouse (liver greater than lung) and rat (liver greater than testis greater than kidney greater than lung greater than striated muscle greater than spleen) S-9 fractions [14].
• In adult fish treated with 1 microM ICR-191 in a water bath for 18 h, a significant increase in MFs was observed in both gill (12 x 10(-5) and 44 x 10(-5) in control and treated fish, respectively), and hepatopancreas (5 x 10(-5) and 29 x 10(-5), respectively) 2 weeks after exposure [15].
• A collection of HLA-DP mutants was generated, using ICR 191 as the mutagenic agent and resistance to lysis mediated by HLA-DPw2 allospecific cytotoxic T lymphocytes (CTLs) as the selection criterion [16].
• Variation of the frameshift activity of a mutagen (ICR-191) following nitrosation in human gastric juice [17].

Associations of ICR 191 with other chemical compounds

• Frame-shift mutants in Namalwa cell cultures were generated with ICR-191, and mutants were then selected for resistance to ricin or resistance to a conjugate of ricin with the anti-CALLA antibody J5 in the presence of lactose [18].
• Accordingly, we have recently observed that base substitutions induced by the acridine half-mustard ICR-191 in the M13 double-stranded DNA transfection system are predominantly G:C-to-A:T transitions [1].
• In contrast, ICR-191 and AFB1 are respectively less than 2 and 3% as efficient as MNNG for OUAr mutant induction relative to the activity of each agent for 6TGr mutagenesis [3].
• 9-Aminoacridine was a potent inducer of +1G, -1G and -1A frameshifts, whereas ICR-191 induced all types of frameshift mutations [19].
• Among the 8-AGr mutants tested, clone ICR-014 or ICR-172 showed a significant increase in reversion frequency over the control level only after treatment with ICR-191 or 2-NF, respectively; but not with the other two mutagens [20].

Gene context of ICR 191

• Reversion to Lac+ promoted by ICR-191 results from the loss of a G residue from a GGG sequence located at the junction of lacZ and IS1 [21].
• (ii) Mutations in mutR can be induced with the frameshift mutagen ICR-191 [22].
• One frameshift strain, hisC3076, also showed increased sensitivity to mutagenesis by ICR-191 when it carried either of two different polA alleles, whereas the hisD3052 and hisC207 frameshifts reduced sensitivity to mutagenesis in the presence of these alleles [23].
• Mutational spectrum of ICR-191 at the hprt locus in human lymphoblastoid cells [24].
• The order of sensitivity to the toxic effect of ICR-191 was MIT-2 greater than WI-L2 greater than GM 130, while the order of sensitivity to the mutagenic effects of this frameshift mutagen was GM 130 greater than MIT-2 greater than WI-L2 [25].

Analytical, diagnostic and therapeutic context of ICR 191

• In addition to these properties, the mutation lacZ::IS1-MS319 has the unique property of reversion to Lac+ (ts) spontaneously or after treatment with the frameshift mutagen ICR-191; such revertants retain the IS1 element [21].
• Southern blot hybridization analyses revealed that most XPRT mutant cell lines which arose following treatment with EMS (20/22) or ICR 191 (20/24) exhibited no alterations of the gpt locus detectable by this technique [26].

References