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Biomedical subjects

K Patil

Publications and source records attributed to K Patil.

At least 55 records · Page 3Linked to original sources
PubMed1980

Tumorigenic action of N-n-butyl-N-formylhydrazine in mice.

Continuous administration of 0.04% N-n-butyl-N-formylhydrazine (BFH) in drinking water to 6-week-old randomly bred Swiss mice for life produced tumors of the lungs, preputial and clitoral glands. The tumor incidences in these three tissues of the treated animals were 87, 66, and 10%, whereas in the untreated controls they were 25, 0, and 0%, respectively. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of the lungs, squamous cell papillomas and carcinomas, angio-, fibro-, and myxo- sarcomas of preputial glands and squamous cell papillomas and carcinomas of clitoral glands. N-n-Butyl-N-formylhydrazine is a structural homologue of the carcinogenic N-methyl-N-formylhydrazine and N-ethyl-N-formylhydrazine. These studies are integral parts of structure activity relationship inquiries.

Animals↗
PubMed1980

Study of the carcinogenicity of large doses of dimethylnitramine, N-nitroso-L-proline, and sodium nitrite administered in drinking water to rats.

Large doses of dimethylnitramine (DMNM), N-nitroso-L-proline (NPRO), and sodium nitrite were administered in the drinking water to MRC Wistar rats for at least 1 year, and the rats were maintained for life. DMNM (total dose, 20 g/kg) produced liver tumors in 25 (69%) of the 36 rats and nasal cavity tumors in 9 (25%) of the rats. NPRO (total dose, 36 g/kg) induced no tumors in 37 treated rats. In the group receiving NaNO2 (3.0 g/liter drinking water; total dose, 63 g/kg), 8 (18%) of 45 rats had forestomach squamous papillomas. The tumor incidence in the NaNO2-treated group was significantly greater than that of 2% in a control group started 11 months earlier, which suggested that the NaNO2 was tumorigenic in this experiment.

Animals↗
PubMed1980

The tumorigenic effect of low dose levels of N-methyl-N-formylhydrazine in mice.

Solutions of 0.002 and 0.001% N-methyl-N-formylhydrazine (MFH) were given separately daily in drinking water to 6-week-old randomly bred Swiss mice for life. The treatments resulted in induction of tumors of the lungs, blood vessels, liver and gall bladder. The 0.002% solution gave rise to tumors of the above tissues in incidences of 76, 27, 28 and 11%, respectively, while the 0.001% solution induced tumors in incidences of 75, 23, 7 and 6%. Histopathologically, the neoplasms were adenomas and adenocarcinomas of lungs, angiomas and angiosarcomas of blood vessells, benign hepatomas, liver cell carcinomas and adenomas and adenocarcinomas of the gall bladder. MFH is an ingredient of the edible mushroom, the false morel Gyromitra esculenta. The present study proves the carcinogenicity of MFH administered at low dose levels. The possible environmental significance of the findings to the human population is discussed.

Animals↗
PubMed1979

False morel mushroom Gyromitra esculenta toxin: N-methyl-N-formylhdrazine carcinogenesis in mice.

N-Methyl-N-formylhydrazine was administered in drinking water as a 0.0039% solution to randomly bred Swiss albino mice for life starting from 6 weeks of age. The compound induced tumors of lungs, livers, blood vessels, gall bladder and bile ducts. The tumor incidences in these five tissues were 77, 46, 21, 10 and 7% while in the untreated controls they were 18, 1, 6, 0 and 0% respectively. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of lungs, benign hepatomas and liver cell carcinomas, angiomas and angiosarcomas of blood vessels, adenomas and adenocarcinomas of gall bladder and cholangiomas. The macroscopic and light microscopic involvement of the tissues with the tumors are described and some of them are illustrated. N-Methyl-N-formylhydrazine is an ingredient of the edible mushroom, the false morel Gyromitra esculenta. The findings are discussed from the viewpoint of a potential human health hazard.

Animals↗
PubMed1979

Carcinogenic effects in the Syrian golden hamster of N-methyl-N-formylhydrazine of the false morel mushroom Gyromitra esculenta.

N-Methyl-N-formylhydrazine (MFH) was administered in drinking water as a 0.0078% solution to randomly bred Syrian golden hamsters for life beginning at 6 weeks of age. The treatment gave rise to benign and malignant liver cell tumors, malignant histiocytomas and tumors of the gall bladder and bile ducts. The tumor incidence in these four treated tissues was 43, 34, 11,8%, while in untreated controls it was 0, 0, 0, 0%, respectively. Histopathologically, tumors were classified as benign hepatomas, liver cell carcinomas, malignant histiocytomas, adenomas and adenocarcinomas of the gall bladder, cholangiomas, and cholangiocarcinomas.

Animals↗
PubMed1979

Carcinogenic potential of hycanthone in mice and hamsters.

Hycanthone was administered to Schistosoma mansoni-infected and non-infected Syrian golden hamsters and Swiss mice by intraperitoneal and intramuscular injection of amounts up to the maximum tolerated dose. No tumors attributable to treatment were observed in hamsters. In infected mice, the overall incidence of hepatomas and hepatocellular carcinomas increased from 3.4% in untreated mice to 10.6% in those treated with hycanthone. Non-infected control mice developed 0.8% of these tumors compared to 10.2% in mice treated with hycanthone. Despite the use of high dose levels of hycanthone, statistical significance was attained only with non-infected female mice injected intraperitoneally and intramuscularly with hycanthone and then only at confidence levels of 92 and 95% respectively.

Animals↗
PubMed1979

Kidney tumors induced in rats by the antischistosomal drug niridazole.

An increased incidence of kidney tumors was found in MRC rats fed the antischistosomal drug niridazole at four dose levels in the diet. Histologically, the adenomas and adenocarcinomas were solid papillary, clear cell, and tubular types, with the latter type predominating. Seven mesenchymal tumors were found among the 107 renal epithelial neoplasms. Severe nephrosclerosis occurred in both treated and control rats and has been suggested as important in renal carcinogenesis. Niridazole is considered a potent inducer of epithelial kidney tumors.

Adenocarcinoma↗
PubMed1978

Carcinogenicity and metabolic profiles of 6-substituted benzo[a]pyrene derivatives on mouse skin.

The ability was tested of appropriate substituents of benzo[a]pyrene (BP) at C-6 to decrease or suppress the carcinogenic activity for these BP derivatives relative to the parent compound. 8-week-old female Swiss mice in 9 groups of 30 were treated on the back with 0.2 mumol of compound in acetone 4 times weekly for 20 weeks. The following compounds were administered: BP, 6-methylbenzo[a]pyrene (BP-6-CH3), 6-hydroxymethylbenzo[a]pyrene (BP-6-CH2OH), benzo[a]pyrene-6-carboxaldehyde (BP-6-CHO), benzo[a]pyrene-6-carboxylic acid, 6-methoxybenzo[a]pyrene, 6-acetoxybenzo[a]pyrene, 6-bromobenzo[a]pyrene, and 6-iodobenzo[a]pyrene. Two additional groups received BP or BP-6-CH3 twice weekly for 20 weeks at a total dose 25% of that above. In addition, the metabolism of selected 6-substituted BP derivatives was studied, using mouse skin homogenates in vitro and mouse skin in vivo. Only four compounds were carcinogenic; the order of potency was BP greater than BP-6-CH3 greater than BP-6-CH2OH and BP-6-CHO. The difference in carcinogenicity between BP-6-CH2OH and BP-6-CHO could not be assessed by this experiment. In a further tumorigenesis experiment the carcinogenicity of BP-6-CH2OH was compared to that of BP-6 CHO, BP-6-CH3 and 6-hydroxymethylbenzo[a]pyrere sulfate ester (BP-6-CH2OSO3Na) on mouse skin. 9-week-old female Swiss mice in groups of 28 were treated at three dose levels with 0.8, 0.2 and 0.05 mumol of compounds in dioxane--dimethyl sulfoxide (75 : 25) twice weekly for 40 weeks. After 40 experimental weeks BP-6-CH2OSO3Na proved to be a more potent carcinogen than BP-6-CH2OH, which, in turn was more active than BP-6-CHO. The greater carcinogenicity of BP-6-CH3 relative to BP-6-CH2OH and BP-6-CHO is confirmed, suggesting that BP-6-CH2OH is not a proximate carcinogenic metabolite for BP-6-CH3. Since BP-6-CHO is a weaker carcinogen than BP-6-CH2OH and is efficiently reduced metabolically to BP-6-CH2OH, the latter compound may be a common proximal carcinogenic metabolite. The stronger potency of BP-6-CH2OSO3Na, compared to its alcohol, suggests that an ester of BP-6-CH2OH might be the ultimate alkylating compound reacting with cellular nucleophiles.

Animals↗
PubMed1978

Carcinogenicity and metabolic profiles of 3-methylcholanthrene oxygenated derivatives at the 1 and 2 positions.

Trapping of 3-methylcholanthrene (MC) radical cation by nucleophilic compounds occurs specifically at the 1-carbon atom. With the purpose of providing more evidence for the hypothesis that the critical mechanism of activation of MC is one-electron oxidation, the carcinogenicity of MC was compared to that of 1-hydroxy-3-methylcholanthrene (MC-1-OH), 3-methylcholanthrene-1-one (MC-1-one), 2-hydroxy-3-methylcholanthrene (MC-2-OH), 3-methylcholanthrene-2-one (MC-2-one) and 3-methylcholanthrylene (MCL) by repeated application on mouse skin. Seven-week-old female Swiss mice in 6 groups of 30 were treated on the back with 0.2 mumol of compound in acetone twice weekly for 20 weeks. In addition, the metabolism of MC and its derivatives was studied using mouse skin homogenates. The compounds tested were classified according to carcinogenicity in 4 groups: MC and MC-2-OH, the strongest carcinogens; MC-2-one and MCL, weaker than MC and MC-2-OH; MC-1-OH, the weakest carcinogen; and MC-1-one, non-carcinogenic. These results support the hypothesis that one-electron oxidation for MC, MC-2-OH and MC-1-one might be the critical mechanism of carcinogenic activation, with C-1 the binding site to cellular nucleophiles. The carcinogenic effect of MC-1-OH is speculated to be the formation of an ester bearing a good leaving group, which might be the ultimate alkylating compound in the in vivo reaction. The lack of carcinogenic activity for MC-1-one may be attributed to absence of nucleophilic trapping at C-1 via the radical cation pathway as well as the inability of mouse skin to reduce MC-1-one to the carcinogenic MC-1-OH.

Animals↗
PubMed1978

Tumor induction with the N'-acetyl derivative of 4-hydroxymethyl-phenylhydrazine, a metabolite of agaritine of Agaricus bisporus.

N'-Acetyl-4-(hydroxymethyl)phenylhydrazine was administered as a 0.0625% solution in drinking water continuously for the life span of Swiss mice, from 6 weeks of age. Compared to that in untreated controls, in treated animals the lung tumor incidence rose from 15 to 34% in females and 22 to 48% in males, whereas the incidence of blood vessel tumors increased from 8 to 32% in females and from 5 to 30% in males. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of the lungs and angiomas and angiosarcomas of the blood vessels. The commonly eaten mushroom Agaricus bisporus contains beta-N-[gamma-L(+)-glutamyl]-4-hydroxymethylphenylhydrazine, which under certain conditions yields 4-hydroxymethylphenylhydrazine and L-glutamic acid. Since 4-hydroxymethylphenylhydrazine is relatively unstable, its acetyl derivative was synthesized for this study. The possible environmental significance of the findings is discussed.

Adenocarcinoma↗
PubMed1977

Tumorigenic effect of 4-methylphenylhydrazine hydrochloride in Swiss mice.

4-Methylphenylhydrazine hydrochloride was administered as 10 weekly subcutaneous injections of 140 microgram/g body weight and as 7 weekly intragastric instillations of 250 microgram/g body weight in physiological saline to randomly bred Swiss mice. Treatments given subcutaneously resulted in induction of lung tumors in incidences of 36% in females and 44% in males, while intragastric treatment caused a 40% incidence in females. In addition, it gave rise to blood vessel tumors by intragastric route in incidences of 32% in females and 18% in males. In the two physiological saline-treated control groups, the lung tumor incidence (combined) was 20% in females and 21% in males, while the blood vessel tumor incidence (combined) was 7% in females and 6% in males. Histopathologically, the lesions were classified as adenomas and adenocarcinomas of the lungs, and angiomas and angiosarcomas of blood vessels. 4-Methylphenylhydrazine was postulated to be a metabolite of 4-hydroxymethylphenylhydrazine, an ingredient of the commonly eaten mushroom Agaricus bisporus. The implications are discussed with respect to the tumorigenesis data.

Animals↗
PubMed1977

Induction of tumors in mice with the herbicide succinic acid 2,2-dimethylhydrazide.

A solution of 2% succinic acid 2,2-dimethylhydrazide was given continuously in the drinking water of 6-week-old randomly bred albino mice for the remainder of their lives. The treatment gave rise to tumors of blood vessels, lungs, and kidneys. The tumor incidences in these tissues in the controls were 6, 18, and 0%, whereas in the treated groups the corresponding tumor incidences were 73, 73, and 5%. Light microscopic examination revealed typical angiomas and angiosarcomas of blood vessels, adenomas and adenocarcinomas of lungs, and adenomas of kidneys. The study thus demonstrates the tumorigenicity of the herbicide, succinic acid 2,2-dimethylhydrazide. Since the residues of this chemical occur in fruit, the human population is exposed to it. The environmental implication of this finding and the fact that the hydrazines as a class have tumorigenic properties are discussed.

Adenocarcinoma↗
PubMed1976

Comparative studies of neoplastic response to a single dose of nitroso compounds. 5. The effect of dimethylnitrosamine in Swiss, ASW/SN and A-strain mice.

The tumorigenic effect of dimethylnitrosamine given once at 5 different dose levels was compared in adult Swiss, ASW/SN and A-strain mice. Considering the overall tumour incidence, at the highest dose level an increase was found in Swiss and ASW/SN mice, but not in A-strain animals. However, the effect of treatment was unequivocal for lung neoplasms. The rate of carcinomas rose significantly in all 3 strains, although a clear dose response-relationship could be established only in Swiss and ASW/SN mice. A dose-dependent effect for adenomas was found solely in Swiss mice.

Adenoma↗
PubMed1975

Isotope effect on the carcinogenicity of 3-methylcholanthrene in mouse skin by selective deuteration of the 1-methylene group: biological evidence for a mechanism of tumor initiation.

3-Methylcholanthrene (MC) in chloroform and trifluoroacetic acid-d1 yielded 3-methylcholanthrene-d4 (MC-d4), a compound selectively deuterated at the 1-, 5-, and 6-carbon atoms. In turn, the protodedeuteration of the labeled hydrocarbon at the 6-carbon atom led to 3-methylcholanthrene-d3 (MC-d3). A comparative test for carcinogenicity between MC and MC-d3 by repeated skin painting on female Swiss mice showed a significantly lower tumorigenic activity of the latter. The result implies that the 1-carbon atom of the hydrocarbon is a critical binding-site to cellular targets in the tumor-initiating process.

Animals↗
PubMed1975

Disappearance of nitrite from the rat stomach: contribution of emptying and other factors.

To help understand how intragastric nitrosation forms N-nitroso compounds, nitriet disappearance from the rat stomach was measured after food containing nitrite was given. In preliminary experiments, nitrite disappearance from buffered aqueous solutions became more rapid as the pH was lowered from 5 to 1 and, at a given pH, was more rapid in a slurry of commercial rat food. The disappearance of nitrite from buffer was little affected by the addition of pepsin, mucin, albumin, or rat gastric contents. When starved rats were given 5 g food with 1.82 mg nANO3/g, nitrate was not reduced to nitrite in the stomach. Five g food containing 154 mug NaNO2/g was administered similarly, and the total stomach (T) and glandular and nonglandular parts (G and NG) were analyzed after 1.5 hours. Weight and nitrite concentration of the stomach contents dropped linearly and the amount of nitrite dropped exponentially (with a half-life of 1.4 hr). Mean nitrite concentration in G was less than half that in NG. From similar experiments with phenol red, emptying accounted for 60% of nitrite loss from T. In G, nitrite concentration was reduced about 3 times due to dilution and 3 times due to other causes. Conditions in G, e.g., nitrite concentration, pH, and empyting time, were discussed in relation to carcinogenesis experiments with nitrite plus amines and amides.

Albumins↗