Effects of the nitro-group on the mutagenicity and toxicity of some benzamines.
The Ames Salmonella/microsomal assay was employed to test the mutagenicity of some benzamines (aniline, and o- and p-phenylenediamine) and their nitro-derivatives (p-nitroaniline, 2-nitro-p-phenylenediamine, 3- and 4-nitro-o-phenylenediamine), using strains TA98 and TA100 and their nitroreductase-deficient mutants, TA98NR and TA100NR, in the presence and absence of rat S9 mix. The addition of the nitro-group to benzamine molecules converted them into direct mutagens. Furthermore, the position of the nitro-group affected their mutagenic activities. Cytotoxicity testing with Chinese hamster ovary cells (CHO-K1) showed that the presence of the nitro-group in these compounds had no specific effect on toxicity. The test compounds all showed a dose-related increase in inducing chromosomal aberrations in CHO cells. However, the presence of the nitro-group did not affect potency in inducing chromosomal aberrations. Compounds containing the nitro-group had higher initial oxidation potentials and dipole moments (mu) than their nonnitro-containing counterparts. The mutagenicity and toxicity of these compounds were not related to physico-chemical properties, including oxidation potential, energy difference (deltaE) between the lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO), ionization potential (I.P.), and mu.
Chung
K T
KT
Division of Molecular Sciences and Microbiology, Department of Biology, University of Memphis, Tennessee 38152, USA.
Murdock
C A
CA
Zhou
Y
Y
Stevens
S E
SE
Li
Y S
YS
Wei
C I
CI
Fernando
S Y
SY
Chou
M W
MW
D000814:Aniline Compounds / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D016466:CHO Cells / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002869:Chromosome Aberrations; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D008297:Male; D015394:Molecular Structure; D009152:Mutagenicity Tests; D009574:Nitro Compounds / Q000737:chemistry / Q000633:toxicity*; D009601:Nitroreductases / Q000172:deficiency / Q000378:metabolism; D010084:Oxidation-Reduction; D010655:Phenylenediamines / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D009574:Nitro Compounds; D010655:Phenylenediamines; D009601:Nitroreductases