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T Ong

Publications and source records attributed to T Ong.

106 records · Page 6Linked to original sources
PubMed1981

Genetic analysis of ad-3 mutants induced by AF-2 and two other nitrofurans in Neurospora crassa.

Our previous studies have shown that the nitrofurans AF-2, SQ18506, and FANFT are potent mutagens in Neurospora crassa. The genetic damage produced by these chemicals at the ad-3 region in N crassa has been characterized by a series of genetic tests. The results of these tests indicate that all three agents induce a high frequency of point mutations and probably a low frequency of multilocus deletions. A comparison of the complementation patterns among the AF-2--induced ad-3B mutants and those induced by other chemical agents indicates that the spectra of intragenic alterations induced by AF-2 in N crassa are similar to those induced by monofunctional alkylating agents.

5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazol↗
PubMed1980

Action of antischistosomal drugs, hycanthone and its analog 1A-4 N-oxide, on viral interferon induction.

Two antischistosomal drugs, hycanthone and its indazole analog 1A-4 N-soxide, of which the former is a potent mutagen, differed markedly in their ability to depress interferon induction by influenza virus in rhesus monkey kidney (LLC-MK2) cell cultures. At the concentration of 10 micron/ml, hycanthone reduced interferon yields as much as 73%; the same quantity of analog had no adverse effect on interferon induction. Pretreatment of cell cultures with the analog negated the inhibitory activity of hycanthone on viral interferon induction; however, this did not occur when the sequence was reversed. Interferon-mediated antiviral cellular resistance was not affected when cell cultures were pretreated with either hycanthone or 1A-4 N-oxide. A possible association may exist between the mutagenicity of antischistosomal drugs and their ability to affect interferon synthesis.

Animals↗
PubMed1980

Genetic analysis of adenine-3 mutants induced by hycanthone, lucanthone and their indazole analogs in Neurospora crassa.

Ad-3 mutants induced by hycanthone, lucanthone and their indazole analogs, IA-3, IA-4 and IA-5 were studied to characterize the genetic alterations produced by these agents in Neurospora crassa. The results of genetic analysis indicate that, in marked contrast to past experiments with chemical mutagens on heterokaryon 12, all of these antischistosomal agents induce a very high frequency of multilocus deletions.

Adenine↗
PubMed1980

Differential effects of cytochrome P450-inducers on promutagen activation capabilities and enzymatic activities of S-9 from rat liver.

Studies have been conducted to determine aryl hydrocarbon hydroxylase, benzphetamine-N-demethylase, epoxide hydrase and glutathione S-transferase activities and cytochrome P-450 content in the liver 9000xg supernatant fractions from rats treated with either phenobarbital, beta-naphthoflavone, ARoclor 1254 or a combination of phenobarbital and beta-naphthoflavone. The metabolic activation of 2-anthramine, 2-acetylaminofluorene, 3-methylcholanthrene, and benzo(a)pyrene to metabolites that are mutagenic in Salmonella typhimurium TA1535 or TA98 by S-9 from rats treated with these inducers was also determined. The induction of drug metabolizing enzymes in the S-9 from Aroclor or phenobarbital plus beta-naphthoflavone treated animals was very similar. The overall results seem to indicate that a combination treatment of phenobarbital and beta-naphthoflavone can be used as a substitute for Aroclor 1254 as inducer for enzyme activity and for the in vitro activation of promutagens to mutagenic metabolites in Salmonella mutagenesis assay systems.

Animals↗
PubMed1979

Genetic effects of PR toxin in eukaryotic microorganisms.

The genetic activity of PR toxin, a mycotoxin from Penicillium roqueforti, was studied in Saccharomyces cerevisiae and Neurospora crassa. The results show that PR toxin, without enzymic activation, causes gene conversion in S. cerevisiae strains D4 and D7, reverse mutation in S. cerevisiae strain D7 and N. crassa strain N24, and mitotic crossing-over in S. cerevisiae strain D7, In the log phase cells of S. cerevisiae the effects are more pronounced at alkaline than at acid pH. The active site responsible for the genetic activity and toxicity is known. The carbonyl groups appear to play an important role in the biologic activity of this molecule.

Chromosomes↗
PubMed1975

Mutagenic evaluation of antischistosomal drugs and their derivatives in Neurospora crassa.

The mutagenic activities of lucanthone, hycanthone, niridazole, and the indazole analogs of lucanthone (IA-3 and IA-5) or hycanthone (IA-4 and IA-6) were studied by assaying for the induction of specific locus mutations in the ad-3 region of N. crassa. The results show that lucanthone, hycanthone, and their indazole analogs (IA-3 through IA-6) are all mutagenic in N. crassa when conidia are treated with any of these compounds. On a per mole basis, hycanthone is the least toxic and mutagenic, whereas IA-3 is the most toxic and mutagenic compound among the six closely related agents. In general, compounds with a methyl group at the C-4 position are more mutagenic than compounds with a methanol group; 6-chloroindazole analogs are more mutagenic and more toxic than nonchlorinated analogs. Niridazole is not mutagenic when conidial suspensions are treated. However, the mutation frequency increased more than 50-fold when niridazole was added to the medium used to grow vegetative cultures. Thus, it appears that the mutagenic activity of this latter compound requires metabolic activation.

Hycanthone↗
PubMed1975

Genetic characterization of adenine-3 mutants induced by 4-nitroquinoline 1-oxide and 4-hydroxyaminoquinoline 1-oxide in Neurospora crassa.

Specific locus mutations induced by the chemical carcinogens, 4-nitroquinoline 1-oxide (4NQO) and 4-hydroxyaminoquinoline 1-oxide (4HAQO), have been characterized to obtain a presumptive identification of the genetic alterations at the molecular level. One hundred eighty-four 4NQO-induced and 219 4HAQO-induced ad-3 mutants of Neurospora crassa obtained in previous studies were studied with a series of genetic tests that permits determination of their genotype and the frequencies of point mutations and multilocus deletions. These tests have shown that the spectrum of ad-3 mutations among 4NQO-induced mutants is similar to that of 4HAQO-induced mutants. None of the 4NQO- or 4HAQO-induced mutants is a multilocus deletion mutant. The ratio of ad-3A to ad-3B mutants is the same in the two samples, as well as the frequencies of complementing ad-3B mutants. These data suggest, then, that the mechanism of mutation induction by 4NQO in N. crassa is identical to that of 4HAQO. It is not clear, however, whether 4NQO is mutagenic per se or reduction of 4NQO to 4HAQO is the first step involved in the mutagenesis of this compound in Neurospora. The heterotaryon tests have shown that the relatively high frequencies of 4NQO- or 4HAQO-induced ad-3B mutants show allelic complementation and that most of the complementing ad-3B mutants (74% of 4NQO induced and 71% of 4HAQO induced) have nonpolarized complementation patterns. From this we conclude that both agents induce predominantly base-pair substitution mutations in N. crassa. The results are in agreement with our other studies which show that potent chemical carcinogens induce predominantly base-pair substitution mutations in N. crassa.

Adenine↗
PubMedDate not supplied

Induction of sister-chromatid exchanges and chromosome aberrations in human peripheral lymphocytes by 2,4,7-trinitro-9-fluorenone.

The genotoxicity of 2,4,7-trinitro-9-fluorenone (TNF) was investigated using the sister-chromatid exchange (SCE) and chromosome aberration assay systems with human peripheral lymphocytes. The SCE frequency increased from the control value of 9.45 to 27.80 (mean of 50 cells scored from each of two donors) after the lymphocytes were treated with the highest dose of TNF (3.0 microgram/ml). The results of the chromosome aberration experiment show that TNF induced more than a 4-fold increase in aberrations in each donor. The results, which indicate that TNF is clastogenic, add further evidence that this compound is potentially genotoxic to exposed populations.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

In vivo cytogenetic studies on mice exposed to ethylene dibromide.

The pesticide, ethylene dibromide (EDB), was evaluated with in vivo cytogenetic assays to determine its genotoxicity. CD1 male mice were exposed to EDB through intraperitoneal injections. Bone marrow cells isolated from femora were analyzed for sister-chromatid exchange (SCE), chromosome aberration and micronucleus formation. The results showed that only certain concentrations of EDB tested caused a slight but significant increase in SCEs and chromosome aberrations. However, these increases were not dose-related. No increase in the polychromatic erythrocytes with micronuclei was observed following EDB exposure. Also, EDB did not cause cell-cycle delay in comparison with controls. Thus, it appears that EDB is not an effective genotoxic agent in vivo in mice.

Animals↗
PubMedDate not supplied

Comparative in vivo and in vitro genotoxicity studies of airborne particle extract in mice.

The genotoxicity of an acetone extract of locally collected airborne particles was evaluated both in vitro and in vivo using the sister-chromatid exchange (SCE) assay in mice. At the highest concentration (5.36 mg/5 ml culture), the extract caused approximately a 3-fold increase in SCEs over controls in mouse bone marrow and spleen primary cells in vitro. However, the same airborne particle extract did not induce a significant increase in the SCE level over controls in vivo in mouse bone marrow and spleen cells when administered intraperitoneally or through oral gavage. This indicates that bone marrow and spleen primary cell cultures can be used in in vitro genotoxicity studies of complex mixtures, and that the genotoxicity of airborne particles detected in the in vitro system cannot always be detected in vivo with the same cell types. In addition, the same acetone extract of airborne particles caused dose-related his+ revertants in the strain TA98 of Salmonella typhimurium, both with and without S9 activation. The significant finding of this study is that the in vitro genotoxicity results of airborne particle extract may not be very meaningful in an in vivo situation.

Air Pollutants↗
PubMedDate not supplied

Mutagenicity and mutagenic specificity of metronidazole and niridazole in Neurospora crassa.

Mutagenicity and mutagenic specificity of niridazole and metronidazole, two chemotherapeutic agents used in the treatment of human parasitic diseases, were studied with the ad-3 test system of Neurospora crassa. The results show that neither compound is mutagenic in resting conidia. In growing vegetative cells, however, both compounds are mutagenic in N. crassa. Genetic analysis of the mutants indicated that niridazole induces predominantly base-pair substitution mutations. None of the niridazole-induced mutants resulted from multilocus deletions. The spectra of genetic alterations induced by metronidazole are similar to those induced by the mono-functional alkylating agents ethyleneimine (EI), ethylmethanesulfonate (EMS), and ICR-177. It is therefore suggested that the mechanism of mutation induction by metronidazole in Neurospora is similar to that of monofunctional alkylating agents.

Genotype↗
PubMedDate not supplied

Mutagenicity and mutagenic specificity of metronidazole and niridazole in Neurospora crassa.

Mutagenicity and mutagenic specificity of niridazole and metronidazole, two chemotherapeutic agents used in the treatment of human parasitic diseases, were studied with the ad-3 test system of Neurospora crassa. The results show that neither compound is mutagenic in resting conidia. In growing vegetative cells, however, both compounds are mutagenic in Neurospora crassa. Genetic analysis of the mutants indicate that niridazole induces predominantly base-pair substitution mutations. None of the niridazole-induced mutants resulted from multilocus deletions. The spectra of genetic alterations induced by metronidazole are similar to those induced by the monofunctional alkylating agents, EI, EMS and ICR-177. It is suggested, therefore, that the mechanism of mutation induction by metronidazole in Neurospora is similar to that of monofunctional alkylating agents.

Genetic Complementation Test↗