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Biomedical subjects

N K Mehrotra

Publications and source records attributed to N K Mehrotra.

At least 37 records · Page 2Linked to original sources
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

Role of GSSG-reductase and a thiol oxidant diethylmaleate (DEM) in skin tumorigenesis induced by jute batching oil.

Single topical application of jute batching oil (JBO-P) elevated the status of enzyme GSSG-reductase in mouse skin and multiple applications produced a persistent increase in the enzyme levels. Also an increase in NADPH-dependent GSSG-reductase activity was registered after single topical application of known carcinogenic polyaromatic hydrocarbons (PAHs), e.g. benzo(a)pyrene (BaP), 7,12-dimethyl-benzanthracene (DMBA) and 3-methylcholanthrene (3-MC). This suggests that the change in GSSG-reductase activity induced by JBO-P is intrinsic to its tumorigenic activity rather than the toxic effect of the oil. Pretreatment of mouse skin with diethylmaleate (DEM), an SH-inactivating agent, increases the latent period of JBO-P induced tumorigenesis. No tumour was recorded in animals belonging to Group IV (DEM + JBO) while in animals belonging to Group II (JBO-P alone) 100% tumorigenesis was recorded during the period of study (i.e. up to 20 wk).

Animals↗
PubMed1989

Tumor initiation in mouse skin by cutting oils.

In order to study the skin tumor-initiating potential for fresh and used cutting oils, a chronic animal bioassay following an initiation-promotion protocol was performed. Tumor initiation was performed by topical application of a single dose of neat fresh/used cutting oil on the mouse skin. After a week, these animals were treated topically with 12-O-tetradecanoylphorbol 13-acetate (TPA), a potent skin tumor promoter. Repeated application of TPA resulted in the appearance of tumors almost at the same time (6-8 weeks) in the groups initiated with fresh or used cutting oil. After a prolonged application of TPA, for 28 weeks, it was observed that the cumulative number of tumors and tumor-bearing animals in the used oil initiated group was slightly less compared to that exposed to a fresh variety of oil. Histopathological examination of the tumors could not show any qualitative differences in the nature of tumors developed in both groups. It seems that both fresh and used cutting oils act as potent skin tumor initiators.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

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↗
PubMed1988

Role of cutaneous GSH in 12-O-tetradecanoyl-phorbol 13-acetate-induced mouse skin tumor promotion.

The role of glutathione (GSH) in skin tumor promotion was ascertained in the present study by investigating the effect of the GSH depletor, diethyl-maleate (DEM), on the tumor-promoting ability of TPA in DMBA-initiated mouse skin. DEM lowered the tumor yield and the tumor incidence by 80% (p less than 0.001) in the DMBA + TPA treated group. The rate of tumor formation was also found to be influenced by DEM. The results suggest that clonal expansion of tumor-initiated cells, stimulated by TPA, depends upon the availability of reduced GSH in the tissue. The mechanism by which depletion of reduced GSH could result in inhibition of skin tumor promotion is not known. However, inactivation of GSH and thus blockage of the physiological function of reduced GSH in the biochemical events obligatory to tumor-cell proliferation in mouse skin could be the possible mechanisms providing effective control over proliferation of tumor cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Teratogenic effects of benzo[a]pyrene in developing chick embryo.

The effect of benzo[a]pyrene (BP), an established carcinogen, on developing chick embryos was investigated. The embryos were exposed in different stages of development to various doses of BP via the yolk sac route. This resulted in retarded growth, as reflected by lower embryonic body weight, reduced crown-rump length and bill length. Abnormal survivors showed remarkably twisted legs with shortening of the bones, abdominal oedema, haematomas, blisters and a short neck. These findings suggest that BP is a teratogen when injected via this route, and the 'oedema syndrome' is a possible mechanism causing teratogenic effects in developing chick embryos when treated with BP.

Abnormalities, Drug-Induced↗
PubMed1988

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↗
PubMed1988

Carcinogenic property of JBO(P) variety of jute batching oil.

The topical application of neat JBO-P variety of jute batching oil (JBO) three times a week has been found to produce skin tumours locally with 13 weeks of treatment on Swiss albino mice. In another set of experiments, 3 times/week topical application of JBO on Swiss albino mouse skin previously initiated (s.c., 1 mg/g body wt.) with urethane resulted in induction of tumours (squamous cell papillomas and keratoacanthomas) in 8 weeks. These results suggest that the JBO-P variety of jute batching oil could be a complete carcinogen or a tumour promoting substance on mouse skin.

Animals↗
PubMed1988

Antagonistic effect of zinc in lead treated developing chick embryos.

Lead (50 micrograms) and zinc (100 & 200 micrograms) alone and in combination, were injected on 7th day of incubation into the yolk sac of developing chick embryos. The deformities induced by Pb alone included reduced hatchability, growth retardation, hydrocephalus, defective beak and legs, microphthalmia, anophthalmia and curling of hair. The concurrent exposure with Zn (200 micrograms), however, provided a remarkable protection against lead induced deformities, reflected in terms of almost normal development of chick embryos with increased hatchability and lower incidences of malformations, and mortality.

Abnormalities, Drug-Induced↗
PubMed1987

Jute batching oil: a tumor promoter on mouse skin.

A mineral oil essentially used in the jute industry for the "batching" of jute fibers, and earlier reported to be nontumorigenic on mouse skin, has been found to be a tumor promoter following a two-stage mouse-skin bioassay protocol. The types of tumors developed after initiation with a single dose of urethane or 3-methylcholanthrene (subcutaneously), followed by repeated skin painting with jute batching oil (JBO) included benign papillomas, keratoacanthomas, and fibrosarcomas. Chemical analysis of this oil indicated the total aromatic content was 11.71% and the amount of fluoranthene, pyrene, chrysene, and triphenylene was in the range of 192.54 to 227.79 mg/kg in the test sample. The underlying biochemical mechanisms for the tumor-promoting effect of JBO seemed to operate through a different pathway rather than involving the induction of cytochrome-dependent monoxygenase and N-demethylase activities in the tissue.

Animals↗
PubMed1987

Effect of butyric acid on 12-O-tetradecanoylphorbol-13-acetate-(TPA) induced mouse skin ornithine decarboxylase (ODC).

Butyric acid was topically applied on the interscapular region of Swiss albino mice before and after application of 12-O-tetradecanoylphorbol-13-acetate (TPA) in various doses and at different time intervals. Skin taken from the painted area, 4 h after TPA application, was subjected to ornithine decarboxylase (ODC) enzyme estimation. It was found that butyric acid inhibited the TPA-induced mouse skin ODC activity. The effect was dependent on the dose and duration of the butyric acid application.

Animals↗
PubMed1987

Protective role of calcium in lead toxicity during development of chick embryo.

In the present study the interaction of lead (Pb) and calcium (Ca) during embryogenesis was investigated. Lead (50 micrograms) alone and in combination with Ca (100 micrograms, 500 micrograms and 1000 micrograms) was injected on seventh day of incubation into the yolk sac of developing chick embryos. Treatment with lead alone caused stunted growth in chick embryos with several deformities e.g. defective beak and legs, hydrocephalus, microphthalmia and anophthalmia. The combined treatment of Pb with Ca showed a remarkable protective effect against lead induced deformities characterized by development of chick embryos with a low incidence of deformities.

Abnormalities, Drug-Induced↗
PubMed1986

Polyaromatic hydrocarbon profile of a mineral oil (JBO-P) by gas chromatography.

The present investigation was aimed at identifying the compound(s) responsible for the carcinogenic activity of a variety of jute batching oil (known as non-FDA variety, pre-FDA variety, or JBO-P), a crude petroleum distillate substantially used in jute industries. This was initially performed by isolating from JBO-P a polyaromatic hydrocarbon (PAH) fraction containing compounds of more than three rings. This fraction was then analysed for its PAH profile by gas chromatography and individual components identified by comparing its flame ionisation detector (FID) signal with those obtained from reference PAHs. The results revealed that PAHs of more than three rings, reported to be a recognised class of chemical carcinogens, were present in the JBO-P sample at the level of 3300 mg/kg of oil (0.33%, w/w); benzo(a)pyrene and dibenz(a,h)anthracene, known to be highly potent carcinogens, constituted 129 mg/kg (0.0129%, w/w) and 29 mg/kg (0.0029%, w/w) of the total oil, respectively; and except for a few signals, the PAH profile of JBO-P was found to be somewhat similar to that reported for a sample of carcinogenic used engine oil.

Chromatography, Gas↗
PubMed1986

Effect of simultaneous exposure to nickel chloride and benzo(a)pyrene on developing chick embryos.

In the present investigation the effect of Benzo(a)pyrene (BP) and Nickel chloride, quite often identified in crude and refined or waste oil, when injected in combination, was investigated on developing chick embryos after exposing them through yolk sac route on 6th day of incubation. Exposure to this combination in different doses resulted in no new deformities other than those experienced in BP treated chick embryos. The mortality and malformations experienced in the chick embryos exposed to BP alone and NiCl2 alone were seen to be added when both the chemicals were simultaneously inoculated into the same chick eggs.

Abnormalities, Drug-Induced↗