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J M Gentile

Publications and source records attributed to J M Gentile.

At least 19 recordsLinked to original sources
PubMed1994

Characterization of 4-nitro-o-phenylenediamine activation by plant systems.

4-Nitro-o-phenylenediamine (NOP) is a powerful direct-acting mutagen which demonstrates significant enhancement in mutagenicity when exposed to plant enzymatic systems. Evidence implicating the involvement of peroxidactic oxidation in NOP activation has been obtained from plant-cell suspension and isolated enzyme experiments. Using selected cytochrome P450 and peroxidase enzyme inhibitors in conjunction with Salmonella typhimurium strain TA98 and intact plant-cell activating systems as well as isolated horseradish peroxidase enzyme we have further investigated NOP activation by plant systems. The activation of NOP by both plant cells and by horseradish peroxidase was suppressed by the P450 inhibitors methimazole and (+)-catechin and by the peroxidase inhibitors diethyldithiocarbamate and potassium cyanide, but was not suppressed by the P450 inhibitors metyrapone and 7,8-benzoflavone. In addition, peroxidase enzymatic activity was measured and found to be inhibited by methimazole, diethyldithiocarbamate and potassium cyanide but not by (+)-catechin. The data strongly support the involvement of exogenous peroxidase in the plant activation of NOP, but point to a complex metabolic system that requires multistep processing before full mutagenic potential of the plant-activated component of NOP is expressed.

Analysis of Variance↗
PubMed1994

Implications for the involvement of the immune system in parasite-associated cancers.

Biological factors can be carcinogenic risk factors in humans and in animals. Numerous theories have been developed to explain the causal link between biologically-associated disease and the ensuing neoplasia. In this paper we discuss the merits of one of these theories, the possible association between the mammalian inflammatory response and cancer.

Animals↗
PubMed1991

International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC publication No. 18. Review of the genotoxicity and carcinogenicity of antischistosomal drugs; is there a case for a study of mutation epidemiology? Report of a task group on mutagenic antischistosomals.

One of the interests of ICPEMC is to identify situations in which the possible induction of inherited defects in man by mutagen exposure could actually be studied. The large-scale use of mutagenic drugs in field programmes against schistosomiasis, mainly during the 1970's, was considered a possible case. An ICPEMC task group approached the problem by (1) updating the genetic toxicology data base for antischistosomal drugs, and (2) reviewing possible study areas. Expertise was combined from genetic toxicology, mutation epidemiology and tropical medicine. It was considered that: (a) if any, hycanthone would be the most appropriate candidate drug for study; (b) it would be virtually impossible to meet the basic requirements of an appropriate mutation epidemiology study, in endemic countries; (c) as more defined genetic endpoints would be selected (e.g. sentinel phenotypes) the required large sample sizes would seem prohibitive, since documentation on past programmes is limited and local demography would render the reliable tracking of substantial numbers of offspring of treated persons an almost impossible task; (d) in most endemic countries proper diagnosis and registration of inherited defects is largely lacking; (e) the problems encountered in demonstrating inherited effects in humans after heavy or chronic exposure to established animal mutagens such as ionizing radiation and cancer chemotherapy, in combination with the ambiguous nature of the animal germ cell data with hycanthone, do not particularly warrant large expectations; (f) since non-mutagenic antischistosomal drugs are now in use, the problem is academic and of low priority in the endemic countries whose medical and research resources are often limited. Thus, studying offspring of hycanthone-treated people to demonstrate the mutagenic potential of the drug in man is not a viable enterprise.

Animals↗
PubMed1989

Effects of specific monooxygenase and oxidase inhibitors on the activation of 2-aminofluorene by plant cells.

Using specific inhibitors, a plant cell/microbe coincubation assay was employed to investigate biochemical mechanisms of plant activation. The biological endpoints of mutation induction, inhibition of mutagenicity and viability of the plant-activating system as well as viability of the microbiological indicator were simultaneously assayed from the same reaction tube. We investigated six inhibitors of monooxygenases and oxidases (diethyldithiocarbamate, methimazole, metyrapone, (+)-catechin, 7,8-benzoflavone and potassium cyanide). The activation of 2-aminofluorene by TX1 cells was mediated by an enzyme system(s) that was inhibited by microM amounts of diethyldithiocarbamate or 7,8-benzoflavone. (+)-Catechin (at low concentrations) or methimazole enhanced the activation of 2-aminofluorene while higher concentrations of (+)-catechin were inhibitory. These data indicate that a significant pathway of the plant activation of 2-aminofluorene is via a cytochrome P-448-type N-hydroxylase. The presence of a FAD-dependent monooxygenase was not detected.

Benzoflavones↗
PubMed1988

The plant cell/microbe coincubation assay for the analysis of plant-activated promutagens.

The preincubation and suspension procedures of the plant cell/microbe coincubation assay are described and the activation of 2-aminofluorene and m-phenylenediamine by cultured tobacco, cotton, carrot and maize cells is compared. The assay measures the plant activation of promutagens into genotoxins detected in Salmonella typhimurium as well as toxicity in plant and microbial cells. At concentrations of 2-aminofluorene 0-0.5 mumoles/reaction tube, the rank order of the efficiency of activation by plant cells was tobacco much greater than cotton greater than carrot. Cultured maize cells did not activate 2-aminofluorene. The tobacco cell activation of 2-aminofluorene was inhibited 50% by 750 microM diethyldithiocarbamate under conditions that did not affect the cell viability. Tobacco cells were also the most efficient plant cells in activating m-phenylenediamine (0-5 mumoles/reaction tube). The 'biological affinity' of m-phenylenediamine for the activation system in tobacco cells was approximately 100 microM.

Biotransformation↗
PubMed1988

The plant activation of m-phenylenediamine by Tradescantia clone 03 and clone 4430 cells in liquid suspension culture.

In this study, we expanded the use of the genus Tradescantia to investigate the plant activation of promutagens and further refine the methodology of the plant cell/microbe coincubation assay. Liquid suspension cell cultures of Tradescantia clone 03 and Tradescantia clone 4430 were used to activate the promutagen m-phenylenediamine into a mutagenic compound which was detected by Salmonella typhimurium strain TA98 in the plant cell/microbe coincubation assay. Optimum treatment parameters were established for both plant cell lines. Optimum was defined as the lowest concentration or shortest time period that provided consistently positive results and high rates of revertants. Preliminary experiments with both cell lines defined 2.5 mumoles m-phenylenediamine per plate as the optimum concentration to be used in the determination of the optimal coincubation period and the optimal concentration of plant cells. These experiments also determined the optimal physiological stage at which both clones should be used in the coincubation assay. Differences were found in the optimal of coincubation (1h for clone 03, 2 h for clone 4430) and growth stage (mid-log for clone 03, mid- to late-log for clone 4430). Similar activation responses were seen for both clones when the concentration of plant cells (mg/ml) was varied. Under optimized conditions, clone 03 cells demonstrated an approximately 10% higher activation response than clone 4430.

Biotransformation↗
PubMed1988

Assessment of the mutagenicity of fractions from s-triazine-treated Zea mays.

A water-soluble extract from maize plants exposed to 3 s-triazine herbicides (atrazine, simazine and cyanazine) has been shown to be mutagenic in strain TA100 of Salmonella. No mutagenic activity was observed in any control plant extracts using either water or a variety of organic solvents. Gel permeation studies of the extracts suggest that the mutagen(s) are small molecules (less than 1000 MW). HPLC fractionation suggests that the mutagens formed from each of the 3 herbicides are similar in polarity and water solubility, eluting in a 50/50 water:methanol fraction. Approximately 89% of 14C-labeled HPLC chromatographable metabolites of atrazine were also associated with this fraction, suggesting a close chemical link between a labeled but unidentified metabolite and the mutagenic activity.

Atrazine↗
PubMed1987

Plant activation of m-phenylenediamine by tobacco, cotton, and carrot cell suspension cultures.

Tobacco, cotton, and carrot plant cell suspension cultures activated the promutagen m-phenylenediamine into a mutagen as detected by Salmonella typhimurium strain TA98 with the use of the plant cell/microbe coincubation assay. For each cell line, mid-log phase plant cells at a density of 100-150 mg/ml were coincubated for 1 hr with concentrations of m-phenylenediamine that ranged from 0.1 to 10 mumol per reaction tube in the preincubation test of the plant cell/microbe coincubation assay. Further experiments were conducted to optimize the activation response for each plant cell line. The density of plant cells in the reaction mixture, the time of coincubation of the reaction mixture, and the stage of the growth curve at which the plant cells were harvested for use in the reaction mixture all affected the response. Experiments that used the conditions determined as optimum for each plant cell line were then conducted. With each cell line, the optimized conditions enhanced the activation response that had been observed with the preliminary conditions. A ranking order based on the concentration-response curves indicated a relationship of tobacco cells much greater than carrot cells greater than cotton cells. Tobacco cells were able to activate m-phenylenediamine into a mutagen at concentrations of less than 10 nmol per plate when using TA98 as the genetic indicator organism. Finally, experiments to determine the type of genetic lesion induced by plant-activated m-phenylenediamine were conducted. By using five of the Ames strains, m-phenylenediamine was shown to be active in inducing revertants in strains TA1538 and TA98 following activation by tobacco cells under the optimized conditions. We conclude that m-phenylenediamine is activated by plant cells into a mutagen that primarily induces frameshift mutations.

Biotransformation↗
PubMed1987

Mutagenicity of selected aniline derivatives to Salmonella following plant activation and mammalian hepatic activation.

We compared several phenylenediamines (4-nitro-o-phenylenediamine, NOP; 2-nitro-p-phenylenediamine, NPD; o-phenylenediamine, OPD; p-phenylenediamine, PPD; m-phenylenediamine, MPD) and aniline (ANL) for mutagenicity to Salmonella directly and following activation by plant and mammalian hepatic S9 using plate incorporation and preincubation protocols. In addition, we assayed each chemical for activation by intact plant cells using the plant cell/microbe coincubation protocol. At the concentrations tested, NOP, NPD, OPD, MPD and ANL were active in one or more assays. NPD, OPD and MPD were activated by mammalian hepatic S9 in one or more assay and each was activated by plant S9 or intact plant cells. ANL was mutagenic only in the presence of plant S9. PPD was not active under any of the test conditions.

Animals↗
PubMed1986

In vitro activation of chemicals by plants: a comparison of techniques.

We have studied the ability of two in vitro plant activation techniques to enhance the mutagenicity of 4-nitro-o-phenylenediamine (NOP) and to activate 2-aminofluorene (2AF). Mutagenic activities of NOP and 2AF were both increased by plant S9 in the Salmonella plate-incorporation and preincubation assays. They were also increased during preincubation with intact plant cells. NOP mutagenic activity was enhanced to a similar extent by plant S9 and by intact plant cells in Salmonella assay, whereas 2AF was activated more extensively by the plant cells than by plant S9. NOP was not enhanced by mammalian hepatic S9 in any assay, whereas 2AF was activated by hepatic S9 under all conditions tested.

Animals↗
PubMed1985

In vitro enhancement of the mutagenicity of 4-nitro-o-phenylenediamine by plant S-9.

The direct-acting mutagen 4-nitro-o-phenylenediamine (NOP) was activated in vitro by pea or tobacco S-9 into a more potent mutagen in Salmonella typhimurium strain TA98. NOP mutagenicity was not altered by Aroclor 1254-induced rat liver S-9. The plant S-9 activation of NOP was heat-sensitive but was not NADPH-dependent, did not involve superoxide radicals, and was not inhibited by CO. A direct relationship between plant peroxidase and NOP activation was established. Several purified peroxidases including horseradish peroxidase, chloroperoxidase, and lactoperoxidase also activated NOP. The perodoxidative process was not H2O2-dependent but was partially inhibited by a peroxidase inhibitor.

Animals↗
PubMed1985

Schistosome related cancers: a possible role for genotoxins.

Schistosomiasis has long been associated with cancer. This association is most prevalent between Schistosoma hematobium and bladder cancer. Numerous theories have been proposed to explain the causal link between the parasite infestation and the ensuing neoplasia. One theory that has not received as much attention as others, however, is the role of genotoxins in the neoplastic process. Considering the substantial amount of supportive evidence for the cocarcinogenic effects of schistosomes, concern for the health effects resulting from exposure of infested individuals to either exogenous or endogenous genotoxins is certainly warranted.

Carcinogens↗