Bacterial mutagenicity of two cyclopentafused isomers of benzpyrene

Two novel cyclopentafused polycyclic aromatic hydrocarbons, naphtho(1,2,3-mno)acephenanthrylene (cyclopenta benzo[e]pyrene) and naphtho(2,1,8-hij)acephenanthrylene (cyclopenta(ij)benzo[a]pyrene) were evaluated for mutagenic activity in the Ames Salmonella typhimurium plate incorporation assay. Both compounds required S9 metabolic activation, and showed optimal activity at low S9 concentrations (below 0.6 mg/plate). Both compounds induced frameshift and base-pair substitution mutations, being active in strains TA98, TA100, TA1537, TA1538 and TA104, but not in strain TA1535. Cyclopenta(ij)benzo[a]pyrene was more active than cyclopentabenzo[e]pyrene, and both were more potent than their parent ring systems, benzo[a]pyrene and benzo[e]pyrene, respectively. Cyclopenta(ij)benzo[a]pyrene was more active in strain TA104 than in TA100 or TA98 (250-470, 340 and 80-100 rev/nmole) as was benzo[a]pyrene (120, 70 and 40 rev/nmole respectively); cyclopentabenzo[e]pyrene was more active in TA100 than TA104 or TA98 (70 versus 50 and 40 rev/nmole), and benzo[e]pyrene showed a similar pattern (4, 3.5 and 0.6 rev/nmole). The relative potencies of the four compounds are in accord with predictions based on perturbational molecular orbital calculations. The peak of activity at low S9 concentrations is consistent with epoxidation at the cyclopentafused ring being the major route of metabolic activation for both these cyclopentafused compounds.     

The bacterial mutagenicity of nitropolychlorinated dibenzo-p-dioxins

The bacterial mutagenicity of 2-nitrodibenzo-p-dioxin, a mixture of 2-nitro-7-chloro- and 2-nitro-8-chlorodibenzo-p-dioxin, 7-nitro-2,3-dichloro-, 8-nitro-2,3,7-trichloro-, 2-nitro-1,3,7,8-tetrachloro- and 3-nitro-1,2,4,7,8-pentachlorodibenzo-p-dioxin was determined using Salmonella typhimurium tester strains TA98 and TA100 with and without rat hepatic S9 for metabolic activation. All the nitro-PCDDs exhibited some direct-acting mutagenicity with both tester strains, however, the activity was significantly lowered in the presence of exogenous S9 and the compounds were more mutagenic to tester strain TA98. The mutagenicity of the nitro-PCDDs was also dependent on structure because there was a marked decrease in activity with increasing chlorine content. Because nitro-PCDDs have recently been identified as incomplete combustion products of municipal waste, this study confirms that this new class of compounds contains some bacterial mutagens.     

Extrapineal N-acetyltransferase activity in rat brain

An extrapineal enzyme that N-acetylates a variety of indole and catechol alkylamines, including the psychoactive drugs mescaline and d-amphetamine, has been partially purified from rat brain. This enzymatic activity has a distinct pH optimum, is linear with incubation time and protein concetration, and is abolished by heating. Purification is approximately ten fold with ammonium sulfate precipitation and column chromatography, yielding a specific activity of 7936 pmoles of product per mg of protein per hour with tryptamine as substrate.     

The regulation of pineal serotonin N-acetyltransferase activity in newborn rats.

Rat pineal serotonin N-acetyltransferase activity increases 2–3 hr after birth and then decreases again. The activity at night is higher than that during the day in rats as young as 1 to 2 days old. Administration of the beta adrenergic blocker trimepranol to newborn or 2-day old rats at night lowers the elevated serotonin N-acetyltransferase activity. Hence, the activity is under adrenergic control even in the not yet innervated pineal gland of the newborn rats.     

Lack of mutagenicity of vinyl chloride in two strains of Neurospora crassa.

No detectable induction of mutations could be found in two strains of Neurospora crassa after their conidia were treated with vinyl chloride, in ethanol solution and in its gaseous form. The results suggest that although N. crassa seems to lativating systems does not increase mutagenic activity of vinyl chloride in the two strains tested. At the same time these strains were mutated easily by UV and methyl methanesulfonate.     

Three consistent patterns of response to substituted acridines in a variety of bacterial tester strains used for mutagenicity testing

91 substituted acridines were tested for mutagenicity in 1 strain of Escherichia coli (TA78) and 4 strains of Salmonella typhimurium (TA90, TA1537, TA98 and TA100). In general, compounds fall into 3 groups: (i) inactive in all strains, (ii) active in TA78, TA90 and TA1537, or (iii) active in TA98 and often one or more of the other frameshift strains. Compounds of class iii have previously been shown to differ from the others in causing excisible damage to DNA and in showing an enhanced mutagenic response when the plasmid pKM101 is present.     

Evaluation of selected alcoholic antiseptics activity against clinical bacterial strains

The aim of this study was to evaluate antimicrobial activity of selected alcoholic antiseptics against clinical strains, which possessed in majority a high level of drug resistance: MRSA (7), MSSA (3), E. coli: (9): strains producing ESBL (4), P. aeruginosa: (4), E. cloacae: (3), K. pneumoniae: (3). These strains were defined by MIC value, using antibiotic agar dilution method according to NCCLS. Fourteen alcoholic antiseptics were used in this study. Beside alcohol, they contained other active substances like iodine, hydrogen peroxide, chlorhexidine. Some additional agents were included for easier application, such as: gelling, moisturizing, aromatic or coloring substances. The objective of this study was also to determine the dependence of bactericidal activity on preparations (concentration). Product undiluted and diluted two and four times in water was analyzed according to prEN 12054 standard; 30 seconds and 1 minute contact time was used. The obtained data indicate that all tested undiluted antiseptics possessed bactericidal activity described by producers. However antiseptics (dilution leads to decrease and even loss of bactericidal activity. Two-times dilution of gel almost completely inactivated the product. Antimicrobial activity after 30 seconds of contact time was not affected by presence of additional agents in the tested antiseptics.     

Isolation and characterisation of bacterial strains containing enantioselective DMSO reductase activity: application to the kinetic resolution of racemic sulfoxides

The kinetic resolution of racemic sulfoxides by dimethyl sulfoxide (DMSO) reductases was investigated with a range of microorganisms. Three bacterial isolates (provisionally identified as Citrobacter braakii, Klebsiella sp. and Serratia sp.) expressing DMSO reductase activity were isolated from environmental samples by anaerobic enrichment with DMSO as terminal electron acceptor. The organisms reduced a diverse range of racemic sulfoxides to yield either residual enantiomer depending upon the strain used. C. braakii DMSO-11 exhibited wide substrate specificity that included dialkyl, diaryl and alkylaryl sulfoxides, and was unique in its ability to reduce the thiosulfinate 1,4-dihydrobenzo-2, 3-dithian-2-oxide. DMSO reductase was purified from the periplasmic fraction of C. braakii DMSO-11 and was used to demonstrate unequivocally that the DMSO reductase was responsible for enantiospecific reductive resolution of racemic sulfoxides.     

Structure-activity relationships of several anisidine and dibenzanthracene isomers in the w/w+ somatic assay of Drosophila melanogaster

Several structurally related anisidine and dibenzanthracene isomers were evaluated for genotoxic effects in the somatic w/w+ assay of Drosophila melanogaster employing insecticide-susceptible (IS) and insecticide-resistant (IR) tester strains. In addition, and in order to find whether or not at the genetic level a regulatory effect is found, crosses between ISxIR strains and IRxIS strains were done. Chemicals tested were the aromatic amines (AAs) ortho-anisidine (o-AN), meta-anisidine (m-AN), and para-anisidine (p-AN) and the polycyclic aromatic hydrocarbons (PAHs) 1,2;3,4-dibenzanthracene (1,2;3,4-DBA) and 1,2;5,6-dibenzanthracene (1,2;5,6-DBA). As positive control N-nitrosodimethylamine (DMN) was used. Our results show that the genotoxic activity of DMN was higher in the IR than in the IS strain. There seems to be a tendency for slightly lower values as measured by clone induction in crosses between ISxIR and IRxIS. o-AN was positive in the IS strain and in crosses between ISxIR and IRxIS but negative in the IR strain. m-AN, p-AN and 1,2;3,4-DBA proved to be not recombinogenic in all strains and crosses while 1,2;5,6-DBA was positive at the highest concentration tested in all the crosses assayed. These findings show that the recombinogenic activity of the anisidine isomers depends on the position of the chemical group relative to one another and that the position of the benzene ring seems to be structurally relevant for genotoxicity of DBA isomers. With respect to IR and IS strains it remains to be determined to what extent the spectrum of metabolizing capacity really differs between the strains of the test assay. Thus more information is needed about the regulation and expression of the cytochrome-P450 genes and action at the molecular level taking place in the eye imaginal disc as well as between insecticide susceptible and resistant strains after exposure to genotoxic chemicals.     

Radiation-induced mutagenicity and lethality in ames tester strains of salmonella

Mutation and killing induced by X radiation and 60CO gamma radiation were studied in six different histidine-requiring auxotrophs of Salmonella typhimurium. Strain TA100, which is sensitive to base-pair substitutions, and strains TA2637 and TA98, which are sensitive to frameshifts, carry the pKM101 plasmid and exhibit significantly higher radiation-induced mutations compared to their plasmidless parent strains TA1535, TA1537, and TA1538, respectively. Among the plasmid-containing strains, TA98 and TA2637 are much more sensitive to the mutagenic action of radiation than is TA100 based on a comparison with their respective spontaneous mutation rates; however, no uniformity was observed in the responses of the strains to the lethal action of ionizing radiation. The pKM101 plasmid provides partial protection against lethality in TA100 and TA2637, whereas the same plasmid enhances the lethal action of ionizing radiation in TA98. The following conclusions are consistent with these observations: (1) the standard Ames Salmonella assay correctly identifies ionizing radiation as a mutagenic agent; (2) frameshift-sensitive parent strains are more sensitive to the mutagenic effects of ionizing radiation than is the only strain studied that is sensitive to base-pair substitutions; and (3) enhancement of mutagenesis and survival is related to plasmid-mediated repair of DNA damage induced by ionizing radiation and does not involve damage induced by Cerenkov-generated uv radiation which is negligible for our irradiation conditions.