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T M Ong

Publications and source records attributed to T M Ong.

53 records · Page 3Linked to original sources
PubMed1981

Mutagenesis at the ad-3A and ad-3B loci in haploid UV-sensitive strains of Neurospora crassa. IV. Comparison of dose-response curves for MNNG, 4NQO and ICR-170 induced inactivation and mutation-induction.

The genetic effects of MNNG, 4NQO and ICR-170 have been compared on 5 different UV-sensitive strains and a standard wild-type strain of Neurospora crassa with regard to inactivation and the induction of forward-mutations at the ad-3A and ad-3B loci. Whereas all UV-sensitive strains (upr-1, uvs-2, uvs-3, uvs-5 and uvs-6) are more sensitive to inactivation by MNNG and ICR-170 than wild-type, only uvs-5 shows survival comparable to wild-type after 4NQO treatment, all other strains are more sensitive to 4NQO. In contrast to the effects on inactivation, a wide variety of effects were found for the induction of ad-3A and ad-3B mutations: higher forward-mutation frequencies than were found in wild-type were obtained after treatment with MNNG or 4NQO for upr-1 and uvs-2, no significant increase over the spontaneous mutation frequency was found with uvs-3 after MNNG, 4NQO or ICR-170 treatment; mutation frequencies comparable to that found in wild-type were obtained with uvs-6 after MNNG, 4NQO or ICR-170 treatment and with upr-1 after ICR-170 treatment. Lower forward-mutation frequencies than were found in wild-type were obtained with uvs-2 after ICR-170 treatment and with uvs-5 after MNNG, 4NQO or ICR-170 treatment. These data clearly show that the process of forward-mutation at the ad-3A and ad-3B loci is under genetic control by mutations at other loci (e.g. upr-1, uvs-2, uvs-3, uvs-5 and uvs-6) and that the effect is markedly mutagen-dependent.

4-Nitroquinoline-1-oxide↗
PubMed1979

Mediated mutagenesis of dimethylnitrosamine in Neurospora crassa by various metabolic activation systems.

Four metabolic activation systems (growth mediated mycelium extract mediated, host mediated, and organ homogenate mediated) were used to study the mutagenic activity of dimethylnitrosamine (DMN) in both forward and reverse mutation systems in the ad-3 (adenine-3) region of Neurospora crassa. DMN was not mutagenic in Neurospora if conidia alone were treated. It was highly mutagenic, however, if conidia were treated with this compound under any of the four activation systems. Quantitative differences in DMN-induced mutation frequencies were observed between in vivo (growth and host mediated) and in vitro (mycelium extract and organ homogenate mediated) activations. The efficiency of the conversion of DMN to a mutagenic metabolite by the organs of rats and mice appeared to be in a reversed order between the host-mediated (liver greater than kidney greater than lung) and the in vitro organ homogenate-mediated (lung greater than kidney greater than liver) assays. Inductions of reverse mutations in strain N23 indicated that DMN induces base-pair substitution in N. crassa.

Animals↗
PubMed1978

Effects of the epoxide hydrase inhibitor, 1,1,1-trichloropropane-2,3-oxide on the genetic activity of aflatoxin B1 metabolites in in vitro activation test systems.

The epoxide hydrase inhibitor 1,1,1-trichloroprophane-2,3-oxide (TCPO) was genetically active to cells of S. cerevisiae and conidia of N. crassa. This genetic activity could be eliminated or reduced to near spontaneous levels in the presence of the S-9 fraction of hamster liver homogenate. The addition of TCPO to an in vitro activation system containing aflatoxin B1 resulted in an increase in the genetic activity of aflatoxin B1, and this increase was dependent on the dose of TCPO. These results are discussed in relation to the possible metabolism of the promutagen aflatoxin B1.

Aflatoxins↗
PubMed1978

Use of the spot, plate and suspension test systems for the detection of the mutagenicity of environmental agents and chemical carcinogens in Neurospora crassa.

N23 and N24, selected from hundreds of ad-3 mutants, have been used as testers for the spot, plate and suspension tests in Neurospora crassa. These two testers are highly sensitive to mutagens and are revertible by a specific group of chemicals. N23 can be reverted from an adenine-dependence to adenine-independence by agents which cause base-pair substitutions whereas N24 can be reverted by frameshift mutagens. Studies described here show that spot, plate and suspension tests using testers N23 and N24 are satisfactory substitutes for the ad-3 forward-mutation system for screening the mutagenic activity of environmental agents and chemical carcinogens in N. crassa.

Bacteriological Techniques↗
PubMed1977

Comparison of the genetic activity of aflatoxins B1 and G1 in Escherichia coli and Saccharomyces cerevisiae.

The ability of aflatoxins B1 and G1 to induce back mutations to arg+ in Escherichia coli K-12/343/113 was compared with the induction of mitotic gene conversion to ade+ in the diploid yeast strain Saccharomyces cerevisiae D4, ade-2. In analogy to previous results with other microorganisms, the compounds were not genetically active per se, indicating that under the experimental conditions employed none of the tester strains were able to activate the compounds to mutagenic products. In experiments using liver homogenates (S-9 fraction) of male Golden Syrian hamsters previously treated with phenobarbital, aflatoxin B1 exhibited strong genetic activity both in E. coli and in S. cerevisiae, whereas the mutagenic activity of aflatoxin G1 was markedly lower and could be detected only in the E. coli tester strain. These results correlate the findings that aflatoxin G1 is a less potent carcinogen and mutagen than aflatoxin B1.

Aflatoxins↗
PubMed1977

Mutation induction by the antischistosomal drug F30066 in various test systems.

The genetic activity of furapromidium (F30066), an antischistosomal drug, was studied in Salmonella typhimurium, Saccharomyces cerevisiae, Neurospora crassa and cultured Chinese hamster cells. The results show that F30066 induces gene mutations in S. typhimurium, N. crassa and Chinese hamster cells. This compound also causes gene conversions in S. cerevisiae.

Acrylamides↗
PubMed1976

Mutation induction by rodent liver microsomal metabolities of aflatoxins B1 and G1 in Neurospora crassa.

The mutagenic activities of aflatoxins B1 and G1 were studied in the ad-3 test system of Neurospora crassa by treatment of conidia with aflatoxin and liver homogenate for 2 h. No significant increase in the ad-3 mutation frequency over the spontaneous frequency was observed when either aflatoxin or mammalian liver homogenate was omitted from the test system. The ad-3 mutation frequencies increased to between 29 and 87/10(6) survivors, which is a 73- to 217-fold increase over the average spontaneous ad-3 mutation frequency (0.4/10(6) survivors), after conidia of N. crassa were treated with 0.67 mM aflatoxin B1, hamster liver homogenate, and a NADPH generating system. A 9- to 15-fold increase in the mutation frequency over the spontaneous mutation frequency was found when 0.67 mM of aflatoxin G1 instead of aflatoxin B1 was used in the test system. Treatment of conidia with 0.44 mM aflatoxin B1 mice liver homogenate and a NADPH generating system caused a small, but significant increase in the ad-3 mutation frequencies. No significant increase in the mutation frequency was found when a single sample of human liver homogenate was used in the test system. These studies show that metabolic activation is necessary for the expression of the mutagenic activity of aflatoxins B1 and G1 in N. crassa.

Aflatoxins↗
PubMed1975

Mutation induction by difunctional alkylating agents in Neurospora crassa.

The genetic characterization of ad-3 mutants of Neurospora crassa induced by two carcinogenic difunctional akylating agents, 1,2,4,5-diepoxypentane (DEP) and 1,2,7,8-diepoxyoctane (DEO), has shown that point mutations at the ad-3B locus have similar complementation patterns. In addition to the induction of point mutations, DEP induces a low frequency (7.5%) of multilocus deletions, whereas DEO induces an extremely high frequency (42.0%). The distribution of the different classes of ad-3 mutants and the frequency of multilocus deletion mutants among DEP-induced mutants are not significantly different from those induced by the monofunctional alkylating agents EI, EMS and ICR-177 at comparable forward-mutation frequencies. Moreover, the frequencies of DEP-induced ad-3B mutants showing allelic completion or having nonpolarized complementation patterns are similar to those of ad-3B mutants induced by monofunctional agents. It is suggested, therefore, that the mechanism of mutation-induction by DEP in N. crassa is similar to that of monofunctional alkylating agents. Mutation-induction by DEO probably results both from the mechanism of action of monofunctional alkylating agents and from inter-strand cross-linkage of the DNA molecular by the two functional epoxy groups.

Adenine↗
PubMed1974

Mutagenic and recombinogenic activities of the food additive furylfuramide in eurkaryotes.

The mutagenic and recombinogenic activities of furylfuramide, an antimicrobial food additive, were tested in a two-component heterokaryon of Neurospora crassa and a diploid strain of Saccharomyces cerevisiae, respectively. The results show that furylfuramide is genetically active in both eukaryotic organisms; it induces mutations in Neurospora crassa and mitotic crossing over in Saccharomyces cerevisiae.

Acrylamides↗
PubMedDate not supplied

Comparison of the genetic activity of 5-nitroimidazole derivatives in Escherichia coli, Neurospora crassa, Saccharomyces cerevisiae and Drosophila melanogaster.

5-nitroimidazoles, including metronidazole (compound 1) and 3 analogues (compounds 2, 3 and 4) of actual or potential chemotherapeutic use were assayed for genetic activity in test systems detecting forward and back mutations in Escherichia coli K-12/343/113, forward mutations in Neurospora crassa heterokaryon 12, mitotic gene conversion in the heteroallelic diploid yeast strain Saccharomyces cerevisiae D4 and sex-linked recessive lethals in Drosophila melanogaster. Whereas metronidazole exhibits moderate mutagenic activity in E. coli, two of the analogues, compounds 2 and 3 are strongly mutagenic even at concentrations that do not inactive the colony forming ability of the cells. The analogue compound 4 does not show any effect toward E. coli under the present experimental conditions. Similar results were obtained with N. crassa, with S. cerevisiae and with Drosophila in which compound 2 exhibits the highest effect, while compound 4 is non-mutagenic in all assays. These biological effects have been partly explained on the basis of differences in the chemical structure of the compounds.

Animals↗
PubMedDate not supplied

Inhibition of methotrexate-induced chromosomal damage by vanillin and chlorophyllin in V79 cells.

Methotrexate (MTX), a chemotherapeutic agent used to treat cancer, produces cytogenetic damage and has a cytostatic effect in a variety of test systems. Several antigenotoxic agents have been studied in various in vitro and in vivo systems. However, data are limited regarding their ability to modulate MTX-induced genotoxicity. In the present study, vanillin (VA) and chlorophyllin (CHL) were used as antigenotoxic agents to study their ability to minimize the DNA damage caused by MTX. Exponentially growing V79 Chinese hamster lung cells were treated with MTX at five different concentrations (5-100 micrograms/ml) with S9 activation for 6 h and post-treated with two concentrations of either VA (50 or 100 micrograms/ml) or CHL (50 or 100 micrograms/ml) for 40 h. Cytochalasin B was added for the micronucleus (MN) assay along with antigenotoxic agents to evaluate MN in binucleated cells. Chromosomal aberrations were also evaluated in parallel cultures. Results indicate that MTX alone induced a dose-dependent decrease in the nuclear division index (NDI) and the mitotic index (MI). A significant increase in percent micronucleated binucleated cells (MNBN) and percent aberrant cells (Abs) was observed. Studies using VA as an antigenotoxic agent showed a decrease in the number of MNBN (26.3-83.1%) and Abs (16.0-87.5%) with the addition of either 50 or 100 micrograms VA/ml. The addition of CHL also significantly reduced the number of MNBN (53.0-91.5%) at both concentrations tested. Chromosomal aberrations were also significantly reduced (41.0-83.0). These studies indicate that both VA and CHL are capable of effectively minimizing MTX-induced chromosomal damage.

Animals↗