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Y Shukla

Publications and source records attributed to Y Shukla.

At least 37 records · Page 2Linked to original sources

Antitumour activity of diallyl sulfide on polycyclic aromatic hydrocarbon-induced mouse skin carcinogenesis.

Diallyl sulfide (DAS), a major flavour component of garlic, is known to modulate xenobiotic metabolism and possess antitoxic, bactericidal, antineoplastic, hypolipidemic and hypocholesteromic effects. In the present study, the anticarcinogenic activity of DAS on a 7,12-dimethylbenzanthracene (DMBA)- or benzo[a]pyrene (B(a)P)-induced mouse skin model of carcinogenesis was evaluated. DAS was applied topically either 1 h prior to or 1 h after the administration of DMBA or B(a)P. A significant protection from neoplasia was observed in DAS- and DMBA/B(a)P-exposed animals when DAS was applied topically compared to the animals exposed only to DMBA/B(a)P. In the animals where DAS was applied 1 h prior to the application of DMBA, a lower magnitude of neoplasia was recorded in terms of the cumulative number of tumours and average number of tumours per mouse during the entire period of study (28 weeks) compared to the animals exposed to DAS 1 h later, while in B(a)P-exposed animals, the antitumorigenic potential of DAS was more evident in the mice treated with DAS 1 h after the B(a)P exposure compared to the animals treated with DAS 1 h prior to B(a)P. The antitumour activity of DAS was of a much higher magnitude in B(a)P-induced carcinogenesis in comparison to animals exposed to DMBA in terms of tumour incidence, cumulative number of tumours and average number of tumours per mouse. The results suggest that DAS has a protective effect in PAH-induced mouse skin carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Carcinogenicity and co-carcinogenicity studies on propoxur in mouse skin.

Propoxur (2-isopropoxyphenyl methylcarbamate) is a widely used broad spectrum carbamate insecticide mainly used to control household pests. Propoxur exposure is reported to inhibit cholinesterase activity in rodents. Apart from other toxic effects, propoxur was found to possess tumorigenic activity in rats after oral administration. Propoxur does not produce tumours in mice or hamsters, or bladder hyperplasia in dogs and monkeys following oral feeding. In this set of investigations the complete carcinogenic, tumour initiating and promoting potential of propoxur was evaluated in male and female Swiss albino mice, since no information was available following dermal exposure of propoxur. The animals were exposed to propoxur through topical painting on the interscapular region at a dose of 100 mg/kg body weight. The results revealed that propoxur has tumour promoting potential on mouse skin following a two-stage initiation-promotion protocol, but it failed to induce the tumour(s) at a significant level, when tested for tumour initiating and complete carcinogenic property.

9,10-Dimethyl-1,2-benzanthracene↗

Chemopreventive effects of black tea polyphenols in mouse skin model of carcinogenesis.

In the present investigations, the antitumorigenic effect of black tea polyphenols (BTP) in two-stage mouse skin model of carcinogenesis was studied. The animals were initiated with a single "subcarcinogenic" topical dose (52 micrograms/200 microliters acetone) of 7, 12-dimethylbenzanthracene (DMBA). To evaluate the anti-tumour initiating activity, BTP was topically applied twice a week for three weeks prior to DMBA application, followed by topical treatment with 12-o-tetradecanoyl phorbol-13-acetate (TPA) (5 micrograms/200 microliters acetone, 2x/wk.) as promoter. For evaluation of antitumor promoting activity, BTP was applied prior to each treatment of TPA. BTP application showed marked inhibitory effect as antitumour initiator as well as antitumour promoter in mouse skin model of two-stage carcinogenesis. Since initiation involves genetic pathway and tumour promotion involves epigenetic pathway, it seems that BTP exerts its antitumorigenic effect by altering both genetic and epigenetic pathways.

Animals↗

Antitumor activity of diallyl sulfide in two-stage mouse skin model of carcinogenesis.

It has been reported that diallyl sulfide (DAS), a sulfur-containing volatile compound in garlic (Allium sativum), exerts anticarcinogenic activity in various rodent tumor models. In the present study, the antitumor property of DAS was tested in Swiss albino mice in the two stage initiation-promotion mouse skin carcinogenesis. Skin cancers were initiated topically with a single subcarcinogenic dose (52 micrograms) of 7, 12-dimethyl benz (a) anthracene (DMBA). Promotion was performed by twice weekly applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) at a dose of 5 micrograms/animal for 32 weeks. DAS was applied topically (250 micrograms/animal) thrice weekly for 3 weeks for anti-initiating and 1 h prior to each promotion treatment for anti-promoting studies. The results showed that the treatment schedule of DAS can effectively delay the onset of tumorigenesis and reduce the cumulative number of tumors and the average number of tumors per mouse. In groups in which DAS applied prior to initiation or promotion, a significant population of the animals remained tumor-free till the termination of experiment. These findings suggest that DAS can effectively inhibit chemically induced mouse skin carcinogenesis.

Administration, Topical↗

Assessment of mutagenic potential of thiram.

Thiram is a widely used dithiocarbamate fungicide. In this study, the mutagenicity of thiram was investigated using the micronucleus and dominant lethal tests in Swiss albino mice. A single ip injection of 100 mg thiram/kg body weight, which is the maximum tolerated dose (MTD), significantly induced micronucleus formation in bone marrow cells after 30 and 48 hr of exposure; 50% and 25% of the MTD also induced micronucleus formation after the above time periods. A significant number of dead implants were induced when thiram was given to male mice in the diet at 10% of the oral LD50 during the whole spermatogenesis cycle (8 wk); this post-implantation loss indicates a dominant lethal mutation.

Animals↗

Antitumour activity of protein A in a mouse skin model of two-stage carcinogenesis.

Protein A (PA) is an immunostimulating glycoprotein (mol. wt. 43,000 kDa) obtained from Staphylococcus aureus cowan I. The antitumour property of PA is well documented in the literature in various transplantable tumours of rats and mice. In the present set of investigations, the antitumour property of PA was tested in Swiss albino mice in a two-stage initiation-promotion mouse skin carcinogenesis model. The animals were initiated topically with a single subcarcinogenic dose (52 microgram) of 7,12-dimethylbenzanthracene (DMBA). PA was administered intraperitoneally (1 microgram/animal), twice weekly for 2 weeks. Promotion was performed by twice weekly applications of 12-O- tetradecanoyl phorbol-13-acetate (TPA) at a dose of 5 microgram/animal for 32 weeks. The result showed that the treatment schedule can effectively check the onset of tumorigenesis, the cumulative number of tumours and the average number of tumours per mouse. In the PA administered group, 30% of the animals remained tumour free until the termination of the experiments (i.e. 32 weeks of promotion). Thus the present study proves that protein A can effectively inhibit DMBA initiated and TPA promoted mouse skin carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Carcinogenic and co-carcinogenic studies of thiram on mouse skin.

Thiram (tetramethyl thiuram disulfide), a carbamate fungicide, is used in the rubber processing industry as an accelerator and vulcanizing agent. Previous studies evaluated the tumorigenic potential of thiram in rodents, but failed to provide conclusive results. In the present study the tumorigenic potential of thiram was evaluated in Swiss albino mice by a two-stage initiation-promotion protocol and a long-term in vivo bioassay for carcinogenicity. Results revealed that following tumour initiation with thiram and promotion with 12-O-tetradecanoyl phorbol 13-acetate, skin tumours developed, mostly at the site of treatment (dorsal skin) in single and multiple dose-initiated animals. Similarly, papillomatous growths were observed on the dorsal skin of the mice initiated with a single subcarcinogenic dose of dimethylbenzanthracene and promoted with thiram. Thiram failed to provoke tumorigenesis when tested as a complete carcinogen for up to 52 wk and thereafter the study was terminated due to increased mortality. It is concluded that thiram has both tumour initiating and tumour-promoting potential in both sexes of Swiss albino mice following topical exposure at the tested dose level.

Administration, Topical↗

Tumour-promoting activity of ninhydrin on mouse skin.

Ninhydrin (2,2-dihydroxy-1,3-indanedione; CAS No. 485-47-2) is widely used as a reagent for the detection of free amino and carboxyl groups in proteins and peptides. It is an irritant to mammalian skin. Various toxic effects of ninhydrin have been reported in laboratory animals; however, so far there has been no evaluation of its carcinogenic and co-carcinogenic potential in laboratory animals by long-term in vivo bioassay. Ninhydrin was found to induce the activity of gamma-glutamyl transpeptidase (GGT) in mouse skin but it failed to alter the activity of the enzyme ornithine decarboxylase when compared with animals treated with standard tumour promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA). In the present investigations, the tumour-promoting activity of ninhydrin (including both stage I and stage II of tumour promotion) was tested on Swiss albino mice in a multistage mouse skin model of carcinogenesis. The animals were initiated with a single topical application of 7,12-dimethylbenz-anthracene followed by four topical applications of ninhydrin biweekly as stage I promoter for 2 wk. Stage II promotion was twice weekly through topical application of mezerein. The results revealed that ninhydrin is a strong stage I tumour promoter and its efficacy was comparable with that of TPA at the dose level used in the experiment. However, ninhydrin failed to produce tumours when tested as a stage II or complete tumour promoter on mouse skin.

9,10-Dimethyl-1,2-benzanthracene↗

Carcinogenic and cocarcinogenic studies with carbaryl following topical exposure in mice.

Carbaryl (1-naphthyl methyl carbamate: C12H11NO2) CAS Reg. No. 63-25-2) is a widely used broad spectrum carbamate insecticide known to exert various toxic effects on experimental animals. Along with various other toxicological effects carbaryl is reported to increase the incidence of neoplasm in various tissues in rats after oral or intraperitoneal administration. No study has so far been reported in rodents to assess its carcinogenic/cocarcinogenic potential after topical exposure. In this set of investigations, the complete carcinogenic, tumour initiating and tumour promoting property of carbaryl was tested on the skin of female Swiss albino mice. The animals were exposed to carbaryl through topical painting on the interscapular region at a dose of 100 mg/kg body wt. The results revealed that carbaryl has tumour initiating potential, at the test dose, on mouse skin following two stage, initiation-promotion protocol, but, it failed to induce the tumour(s) when tested for complete carcinogenic and tumour promoting properties.

9,10-Dimethyl-1,2-benzanthracene↗

Protection against 7,12-dimethylbenzanthracene-induced tumour initiation by protein A in mouse skin.

Protein A is an immunostimulating glycoprotein obtained from Staphylococcus aureus Cowan I. Its antitumour activity is proven in various tumour models. Its ability to provide protection against tumour initiation by the chemical carcinogen 7,12-dimethylbenzanthracene (DMBA) has been investigated in the present study using a mouse skin model of two-stage carcinogenesis. Protein A was administered intraperitoneally (1 microgram/animal 20 g body wt.) twice a week for 2 weeks, prior to initiation by DMBA. The promotion was performed by twice weekly applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) (3 or 5 micrograms/animal in 100 microliters acetone). Protein A provided significant protection to animals from DMBA-induced tumour initiation as was observed by the decrease in cumulative number of tumours, percent of animals developing tumours, number of tumours per animal and rate of tumour growth. Our data indicate that protein A has anticarcinogenic properties.

9,10-Dimethyl-1,2-benzanthracene↗

Carcinogenic activity of a carbamate fungicide, mancozeb on mouse skin.

Mancozeb, a polymeric complex of ethylene bis (dithiocarbamate) manganese with zinc salt is a protective fungicide. In the present study complete carcinogenic activity of mancozeb, has been observed following topical application on dorsal mouse skin. Female Swiss albino mice were exposed to mancozeb at a dose of 100 mg/kg body weight dissolved in 100 microliters dimethyl sulfoxide 3 times per week. Development of tumours was observed after 31 weeks (217 days) of mancozeb application. A high rate of mortality was observed after 54 weeks (378 days) of mancozeb application due to its toxicity and the study was terminated after 60 weeks. On histological examination, these tumours were found mostly to be benign in nature, e.g., squamous cell papillomas and keratoacanthomas.

Administration, Topical↗

Tumour initiatory activity of a herbicide diuron on mouse skin.

In the present investigation, the tumour initiating activity of a herbicide diuron 3-(3,4 dichlorophenyl)-1,1 dimethyl urea has been observed following multiple topical applications at a dose of 250 mg/kg body weight in a standard two-stage initiation-promotion protocol on mouse skin for carcinogenicity testing. It was found that 9 applications of the herbicide given on the interscapular region in a thrice weekly schedule up to 3 weeks and followed, after 1 week, by the repeated 3 times per week application of a known skin tumour promoter 12-O-tetradecanoyl phorbol 13-acetate (TPA), 5 micrograms dissolved in 100 microliters of acetone in the same initiated area, led to the development of benign skin tumours. However, a single dose of diuron, used for each application as above and followed by repeated TPA applications, with the same dose and painting schedule as in the case of multiple applications, failed to initiate tumour development.

Animals↗

Evaluation of carcinogenic effect of jute batching oil (JBO-P) fractions following topical application to mouse skin.

Jute batching oil (JBO-P), a mineral oil fraction used in the processing of jute fibers, was, as reported in our earlier studies, found to be tumorigenic following repeated topical application to mouse skin. In the present investigation an attempt has been made to identify the carcinogenic constituents of this oil. The JBO was fractionated into (1) PAH free fraction, (2) fraction containing two- and three-ring PAHs and (3) more than three-ring PAH fractions by an enrichment procedure. These three JBO fractions along with unfractionated and reconstituted oil were then subjected to the in vivo assay of complete carcinogenic activity of JBO-P and its fractions following its topical application to mouse skin. The results showed that only unfractionated and reconstituted JBO-P samples per se were able to produce benign skin tumours, while all the other three fractions, i.e. PAH-free fraction, two- and three-ring PAH-containing fraction and more than three-ring PAH-containing fraction failed to produce tumours up to 40 weeks after application. In an extended study, mice belonging to the groups exposed to various fractions of JBO were promoted with 12-O-tetradecanoyl phorbol-13-acetate (TPA), a potent skin tumour promoter, for the two stage initiation-promotion protocol for skin carcinogenesis. After 14 weeks of promotion with TPA, all the surviving animals exposed to the fraction having more than three-ring PAHs developed benign tumours on their backs, while the other two fractions failed to do so.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Tumour-promoting ability of mancozeb, a carbamate fungicide, on mouse skin.

In this study the tumour-promoting activity of a carbamate fungicide, mancozeb, has been observed following topical application on mouse skin in a two-stage initiation--promotion protocol for carcinogenesis. Female Swiss albino mice were initiated with a single subcarcinogenic dose (52 micrograms) of 7,12-dimethylbenz[a]anthracene painted on the interscapular region. Seven days after initiation the mice underwent topical application of mancozeb (100 mg/kg body wt) three times per week as promoter. Development of tumours was observed after 12 weeks of mancozeb application in 1/14 animals and 100% tumorigenesis was recorded after 17 weeks of mancozeb application. On histological examination, these tumours were found mostly to be benign in nature, e.g. squamous cell papillomas and keratocanthomas.

9,10-Dimethyl-1,2-benzanthracene↗