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Relationships between structures and mutagenic potencies of 16 heterocyclic nitrogen mustards (ICR compounds) in Salmonella typhimurium.
Mutat Res. 1984 Jun; 136(3):185-99.MR

Abstract

16 heterocyclic nitrogen mustards (ICR compounds), which were synthesized for use as possible antitumor agents by Creech and coworkers, were tested for mutagenicity in Salmonella typhimurium strains TA1535, TA1536, TA1537, TA1538, TA98 and TA100. The compounds were incorporated into the top agar at 5 doses: 0.5, 1, 2.5, 5 and 10 micrograms/plate. All of the compounds were negative in TA1535 except ICR 449, which was positive in all 6 strains. The other 15 compounds were positive in the remaining strains with the following exceptions: ICR 371 and 355 were negative in TA100; ICR 445 was negative in TA98 and TA100; and ICR 360 was negative in TA1537, TA1538, TA98 and TA100. Good qualitative agreement was observed between the mutagenic and antitumor activities of the 16 compounds, and between the mutagenic and carcinogenic activities of the 5 compounds that have been tested for carcinogenicity by Peck and coworkers. However, no significant correlation was found between mutagenic potency in Salmonella and antitumor potency in mice for the 16 compounds. Also, for the 5 compounds that have been tested for carcinogenicity, no significant correlation was found between their mutagenic potency in Salmonella and their carcinogenic potency in mice. In Salmonella, the secondary (2 degrees) amines generally were more mutagenic than their tertiary (3 degrees) amine homologs, although the opposite result has been reported in certain eukaryotes. Relationships between structures and potencies for the different nuclei of the 16 ICR compounds are discussed, as are similarities and differences in strain sensitivities. We conclude that the Salmonella his reversion test is not a good predictor of the antitumor and carcinogenic potencies of these ICR compounds.

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Authors

DeMarini DM
No affiliation info available
Pham HN
No affiliation info available
Katz AJ
No affiliation info available
Brockman HE
No affiliation info available

MeSH

AdenomaAminoacridinesAnimalsAntineoplastic AgentsCarcinogensCarcinoma, Ehrlich TumorDrug Evaluation, PreclinicalFemaleLung NeoplasmsMiceMice, Inbred StrainsMutagenicity TestsMutagensMutationNitrogen Mustard CompoundsSalmonella typhimuriumSpecies SpecificityStructure-Activity Relationship

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

6204200

Citation

DeMarini, D M., et al. "Relationships Between Structures and Mutagenic Potencies of 16 Heterocyclic Nitrogen Mustards (ICR Compounds) in Salmonella Typhimurium." Mutation Research, vol. 136, no. 3, 1984, pp. 185-99.
DeMarini DM, Pham HN, Katz AJ, et al. Relationships between structures and mutagenic potencies of 16 heterocyclic nitrogen mustards (ICR compounds) in Salmonella typhimurium. Mutat Res. 1984;136(3):185-99.
DeMarini, D. M., Pham, H. N., Katz, A. J., & Brockman, H. E. (1984). Relationships between structures and mutagenic potencies of 16 heterocyclic nitrogen mustards (ICR compounds) in Salmonella typhimurium. Mutation Research, 136(3), 185-99.
DeMarini DM, et al. Relationships Between Structures and Mutagenic Potencies of 16 Heterocyclic Nitrogen Mustards (ICR Compounds) in Salmonella Typhimurium. Mutat Res. 1984;136(3):185-99. PubMed PMID: 6204200.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relationships between structures and mutagenic potencies of 16 heterocyclic nitrogen mustards (ICR compounds) in Salmonella typhimurium. AU - DeMarini,D M, AU - Pham,H N, AU - Katz,A J, AU - Brockman,H E, PY - 1984/6/1/pubmed PY - 1984/6/1/medline PY - 1984/6/1/entrez SP - 185 EP - 99 JF - Mutation research JO - Mutat Res VL - 136 IS - 3 N2 - 16 heterocyclic nitrogen mustards (ICR compounds), which were synthesized for use as possible antitumor agents by Creech and coworkers, were tested for mutagenicity in Salmonella typhimurium strains TA1535, TA1536, TA1537, TA1538, TA98 and TA100. The compounds were incorporated into the top agar at 5 doses: 0.5, 1, 2.5, 5 and 10 micrograms/plate. All of the compounds were negative in TA1535 except ICR 449, which was positive in all 6 strains. The other 15 compounds were positive in the remaining strains with the following exceptions: ICR 371 and 355 were negative in TA100; ICR 445 was negative in TA98 and TA100; and ICR 360 was negative in TA1537, TA1538, TA98 and TA100. Good qualitative agreement was observed between the mutagenic and antitumor activities of the 16 compounds, and between the mutagenic and carcinogenic activities of the 5 compounds that have been tested for carcinogenicity by Peck and coworkers. However, no significant correlation was found between mutagenic potency in Salmonella and antitumor potency in mice for the 16 compounds. Also, for the 5 compounds that have been tested for carcinogenicity, no significant correlation was found between their mutagenic potency in Salmonella and their carcinogenic potency in mice. In Salmonella, the secondary (2 degrees) amines generally were more mutagenic than their tertiary (3 degrees) amine homologs, although the opposite result has been reported in certain eukaryotes. Relationships between structures and potencies for the different nuclei of the 16 ICR compounds are discussed, as are similarities and differences in strain sensitivities. We conclude that the Salmonella his reversion test is not a good predictor of the antitumor and carcinogenic potencies of these ICR compounds. SN - 0027-5107 UR - https://www.unboundmedicine.com/medline/citation/6204200/Relationships_between_structures_and_mutagenic_potencies_of_16_heterocyclic_nitrogen_mustards__ICR_compounds__in_Salmonella_typhimurium_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0165-1218(84)90052-1 DB - PRIME DP - Unbound Medicine ER -