Mary Antony

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.

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.

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.

Inhibition of mouse skin tumor promotion by tenuazonic acid

Tenuazonic acid (TA) was topically applied to the interscapular region of Swiss albino mice at different doses before the application of 12-O-tetradecanoyl phorbol-13-acetate (TPA). Skin from the painted area was examined for ornithine decarboxylase (ODC) enzyme estimation. It was observed that TA inhibited TPA induced ODC activity. The inhibitory effect of TA was also found in mouse skin tumor promotion in the two stage initiation promotion protocol. There was a remarkable delay in the latency period and decrease in the number of tumors developed and the percentage of tumor bearing animals after TA treatment.

Oxidised glutathione reductase activity in mouse epidermis: TPA induced change and its modulation by vitamin A.

Single cutaneous application of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) increased epidermal oxidised glutathione reductase activity in adult mouse by almost 100%. Pretreatment of animals with vitamin A for a week resulted in 75% inhibition of TPA induced change in the enzyme activity which remained unaffected in skin treated with vitamin A alone. This biochemical change in skin induced by TPA and modulated by vitamin A has been discussed in relation to epidermal hyperplasia.

Induction of benzo[a]pyrene hydroxylase in skin and liver by cutaneous application of jute batching oil.

Skin painting with 30 microliter of jute batching oil (JBO) for 8 days resulted in increased gross liver weight, microsomal protein content and benzo[alpha]pyrene hydroxylase activity of liver. Skin benzo[alpha]pyrene hydroxylase activity at the treated site increased by 10-fold. An investigation of cytochrome pigment status in liver and skin of treated animals showed a specific increase in P-448 level in both tissues. Single skin applications of JBO elevated the level of skin and liver benzo[alpha]pyrene hydroxylase activity to its maximum after 1 day and 2 days, respectively, which, in absence of further treatment with mineral oil, declined gradually to normal levels in due course. The results suggest that single or multiple cutaneous exposure(s) with JBO can increase carcinogen metabolising status of skin and liver which may be one of the causative factors for the tumorigenic effects of JBO in skin.

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.

Quantification of tumour initiating effect of jute batching oil and its distillates over mouse skin

In order to identify the tumour initiating constituent(s) of a mineral oil, jute batching oil (JBO), used in the processing of jute fibres, it was fractionally distilled in various boiling range fractions. The latter were then subjected to in vivo assessment of their aryl hydrocarbon hydroxylase (AHH) inducing potential in mouse epidermis. Fractions with almost similar AHH inducing potential were regrouped and studied for their tumour initiating potential over mouse skin following two-stage initiation-promotion protocol and using 12-O-tetradecanoyl phorbol-13-acetate (TPA) as tumour promoter. It was noticed that: (1) JBO as initiator, provoked local development of benign skin tumours over mouse back; (2) fractions of JBO boiling below 335 degrees C and above 399 degrees C accounted for most of the tumour initiating potential of the oil; (3) the histological features of the tumours (i.e. benign papillomas and keratoacanthomas) initiated by these fractions were similar to those developed after being initiated with unfractionated or reconstituted JBO; (4) removal of these fractions from JBO may be attempted which could decontaminate the batch oil from most of its tumorigenic components and make it safer for industrial use.

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

SummaryThe role of glutathione (GSH) in skin tumor promotion was ascertained in the present study by investigating the effect of the GSH depletor, diethylmaleate (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<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.

Evaluation of some enzyme markers for diuron toxicity after oral exposure in rats.

Abstract Diuron is a herbicide that inhibits the rate of photosynthesis and is used for general weed control. In the present investigation, the toxicity of diuron (technical grade) was tested at low (35 ppm) and high (70 ppm) dose levels in adult female rats, after feeding the herbicide for 30 days. The results indicate a significant increase in γ-glutamyl transpeptidase activity in serum and liver at both doses. The activity of glutamic oxaloacetic transaminase and glutamic oxalopyruvic transaminase showed an increase in liver, while the activity of these enzymes was significantly elevated in serum of the exposed rats indicative of hepatotoxicity.