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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early mucosal changes of the glandular stomach in Wistar rats ingesting N-methyl-N'-nitro-N-nitrosoguanidine were studied. Special attention was paid to clarifying the localization and chronological relationship between the expected regenerative changes and the succeeding carcinoma. For this purpose, drinking water of MNNG at a low concentration was given to the inbred Wistar rats which were sacrificed every second week during the first 35 weeks. In the 5th week, localized erosions appeared, which were constantly observed through about the 20th week. These changes were always located near the midpoint of the lesser curvature. Epithelial cells, which were found there, were studied with light and electron microscope, and with enzyme histochemistry. It has been observed that these cells corresponded with the so-called immature cells in the normal gastric epithelium and also with the regenerating epithelial cells, which were obtained from the vicinity of mechanically induced ulcer of the stomach. From about the 20th week 2 cases showing ectopic gland, 4 adenomatous changes, 2 early carcinomas, and 5 invasive carcinomas were found. All these lesions were located on the lesser curvature, near its midpoint, i.e. exactly the same area where regularly the erosions were observed.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1976
PMID:Early changes of glandular stomach in Wistar rats ingesting N-methyl-N'-nitro-N-nitrosoguanidine (MNNG): with special reference to light microscopic, electron microscopic, and enzyme histochemical study of the regenerating epithelium induced by MNNG. 13 21

Variations in epidermal chalones after a single surface application of methylcholanthrene have been described in previous papers. This paper reports a study of the effect of croton oil on epidermal growth regulators (G1 and G2 chalones). Hairless mice received a single topical application of 0.2 ml 0.25% acetone solution of croton oil. Control mice received only acetone. The short-term effect of croton oil on epidermal DNA synthesis and mitotic rate was studied. Other groups of croton oil-treated and acetone-treated mice were then killed at similar time intervals, and the treated area of skin was homogenized and extracted with water. The inhibitory effect of these extracts on normal epidermal DNA synthesis and mitotic rate was assayed in normal hairless mice. The resulting inhibition was interpreted as an expression of the concentration of G1 and G2 chalones, respectively, in the skin extracts. The first experiment confirmed that a single croton oil application provokes a short block in epidermal mitotic activity and probably also in DNA synthesis. This was followed by bimodal peaks of increased activity, the two maxima of mitotic rate on days 2 and 7. The concentration of the two chalones in the skins of treated animals varied in inverse proportion to the alterations in the DNA synthesis and the mitotic rate, with one exception. There was here initially a depression both of the mitotic rate and a low concentration of G2 chalone. This was interpreted as a short, initial direct effect of croton oil on the G2 chalone present at the time of application. It is concluded that croton oil application injures and kills epidermal cells, with subsequent alterations in the content of G1 and G2 chalones. This theory may explain the changes observed. The effects of croton oil on the amount of G1 and G2 chalones in the skin are probably related to the direct, toxic, cell-killing effect of croton oil, and not to its specific cancer promoting potency.
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PMID:Effects of croton oil on epidermal growth regulators (chalones). 13 13

Separate solutions of 0.015% benzylhydrazine dihydrochloride and 0.01% phenylhydrazine hydrochloride were given continuously in the drinking water of 6- and 5-week-old randomly bred Swiss mice for the remainder of their life. The consumption of benzylhydrazine dihydrochloride significantly increased the lung tumor incidence from 21 to 42% in the females, while in phenylhydrazine hydrochloride-treated mice, the incidence of blood vessel tumors rose significanly from 5 to 22% in females and from 6 to 20% in males, as compared with the controls. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of lungs and angiomas and angiosarcomas of blood vessels. The study thus proves for the first time the tumorigenicity of benzylhydrazine dihydrochloride. It also confirms the tumor inducing ability of phenylhydrazine hydrochloride, which is used in medicine for treatment of polycythemia vera.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1976 Dec 09
PMID:Tumorigenic effects of chronic administration of benzylhydrazine dihydrochloride and phenylhydrazine hydrochloride in Swiss mice. 13 72

1-(2-Chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (GANU), a water-soluble nitrosourea, differs from 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (chlorozotocin) by the placement of the cytotoxic group on C-1 of glucose. Its biological and biochemical properties are compared with those of chlorozotocin. At a 10% lethal dose (10 mg/kg i.p.), GANU demonstrates minimal myelosuppression. This dose failed to depress normal bone marrow DNA synthesis, in contrast to a 96% inhibition in L1210 DNA synthesis. In L1210 cell suspension, equimolar doses of GANU and chlorozotocin produced equivalent degrees of inhibition in DNA synthesis. GANU has significant L1210 activity in BALB/c X DBA/2 F1 mice treated on Day 2 of tumor growth. A 117% increased life-span and 15% 45-day survivors are atained with 15 mg/kg i.p., a 50% lethal dose. However, in concurrent studies using randomly selected littermate groups of mice, GANU proved less active than chlorozotocin which produced a 306% increased life-span (15 mg/kg i.p.). GANU and chlorozotocin have similar in vitro alkylating activity but the in vitro carbamoylating activity of GANU is sevenfold that of chlorozotocin. On a molar basis, the lethal toxicity of GANU is twice that of chlorozotocin. The significant carbamoylating activity of GANU may contribute to its greater toxicity and therefore limit the mumoles of alkylating agent that can be administered to the tumor. These structure-activity studies further confirm that the addition of a glucose carrier to a cytotoxic nitrosourea moiety can selectively reduce bone marrow toxicity while retaining antitumor activity.
Cancer Res 1977 Mar
PMID:Biological and biochemical properties of 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (NSC D 254157), a nitrosourea with reduced bone marrow toxicity. 13 78

Substitution with a methyl group in the 2-, 3- or 4-position respectively of the phenyl moiety of N-methyl-N-nitrosobenzylamine results in a considerable reduction of the acute toxicity. (LD 50 of MNBA: 18 mg/kg (Druckrey et al., 1967), 2-Me-MNBA: 90 mg/kg, 3-Me-MNBA: 600 mg/kg, 4-Me-MNBA: 400 mg/kg). However, the introduction of the methyl group influences the carcinogenic activity of MNBA in rats and its organotropy, only to a small extent. Long-term administration of 5 and 15 ppm respectively of the isomeric N-nitroso compounds in the drinking water produces in all animals carcinomas of the oesophagus and the pharynx.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1977
PMID:[Change of toxicity and carcinogenicity of N-methyl-N-nitrosobenzylamine in rats by methylsubstitution in the phenylresidue]. 14 May 40

The aim of the experiments was to determine whether the various types of carcinomas found in the human urinary bladder were reproducible in animals. We added n-butyl-n-(4-hydroxybutyl)-nitrosamine at a dose of 20 mg/kg/day to the drinking water of 177 female Wistar rats for a period of 40 to 150 days. After a total experimental time of between 150 and 250 days the animals were sacrified. The spectrum of carcinomas induced, includes all the types known to occur in man. The various tumor types occurred with the same frequency as in man and exhibited the same growth patterns. Variously differentiated papillary and non-papillary transitional cell carcinomas comprised 88.8% of tumors registered. 5.1% were keratinized and nonkeratinized squamous cell carcinomas, 2.2% adenocarcinomas. 1.1% were undifferentiated carcinomas and 2.8% were carcinomas of the mixed type with squamous cell and transitional cell differentiation. Histogenetically adenocarcinomas were found to originate from glandular metaplasia and squamous cell carcinomas from squamous metaplasia within completely developed transitional cell carcinomas. Furthermore it was possible to induce proliferative lesions such as von Brunn's nests, cystitis cystica and cystitis glandularis. However, we found no clues to substantiate the development of adenocarcinomas from these proliferative lesions, or for that matter squamous cell carcinomas from squamous metaplasia of the otherwise unchanged urothelium. The present experimental model seems particulary suited for the search of further information regarding the development of tumors in the human bladder.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1977
PMID:Morphology, classification and histogenesis of N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced carcinomas in the urinary bladder of rats. 14 May 44

Four nitrosamines; nitroso-N-methylpiperazine, 2,3,5,6-tetramethyldinitrosopiperazine, nitrosoisonipecotic acid and nitrosomethoxymethylamine, closely related in structure to potent carcinogens, were fed chronically to rats in drinking water for one year. No toxic effects leading to life shortening were observed. There was no significant incidence of any malignant tumor other than the endocrine tumors normally found in untreated animals of our colony. This indicated that the small changes in structure represented by these compounds were sufficient to reduce greatly, or eliminate, the carcinogenic action.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1977 May 20
PMID:Carcinogenesis tests of nitroso-N-methylpiperazine, 2,3,5,6-tetramethyldinitrosopiperazine, nitrosoisonipecotic acid and nitrosomethoxymethylamine in rats. 14 97

1-Nitrosopiperazine was fed to two groups of rats as drinking water solutions containing 400 mg/liter (3.5 millimolar) and 800 mg/liter (7.0 millimolar), respectively. The treatment was 20 ml per rat per day, 5 days per week for life. In both groups many animals died with olfactory tumors (mostly esthesioneuroblastomas), the first at 36 weeks in the higher dose group, the first at 64 weeks in the lower dose group. There was also a small number of liver tumors in both groups. None of these tumors was seen in the untreated controls. The similarity of this tumor distribution to that produced by 1,4-dinitrosopiperazine suggests that the observed carcinogenicity of 1-nitrosopiperazine may be entirely due to its disproportionation in the acidic medium of the rat stomach. Chemical data supporting this interpretation are presented.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1977 May 20
PMID:Chronic oral administration of 1-nitrosopiperazine at high doses to MRC rats. 14 2

1-4-Amino-2-methylpyrimidin-5-yl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) is a water-soluble nitrosourea that has produced delayed hematological toxicity in man during Phase 1 clinical trials. ACNU has in vitro alkylating activy 40% less than that of 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (chlorozotocin) but shares the property of negligible carbamoylating activity with the latter compounds. ACNU is highly active against murine L1210 leukemia. However, the maximum therapeutic dose, 30 mg/kg (a dose lethal to 10% of the animals), produced a 64% reduction in peripheral WBC and an 85% decrease in circulating neutrophils in normal mice. This was correlated with a 76% inhibition of normal mouse bone marrow DNA synthesis within 24 hr after treatment, followed by full recovery within 48 hr after treatment, followed by full recovery within 48 hr. In contrast, DNA synthesis in L1210 cells was suppressed to less than 10% of control for a minimum of 72 hr. While ACNU, a pyrimidine analog, possesses many of the chemical properties of chlorozotocin, it does not share with the latter compound its reduced myelotoxicity at therapeutic doses. The glucose carrier of the chlorozotocin molecule appears to impart the selective sparing of normal bone marrow.
Cancer Res 1978 Jan
PMID:A comparison of the biological and biochemical properties of 1-(4-amino-2-methylpyrimidin-5-yl)methyl-3-(2-chloroethyl)-3-nitrosourea and 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose. 14 14

The lethal and bone marrow toxicity and antitumor activity of the cis- and trans-2-hydroxylated metabolites of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) have been correlated with their relative in vitro alkylating and carbamoylating activities. Both the isomers have considerably greater alkylating activity and shorter chemical half-lives than the parent compound and on a molar basis have greater antitumor activity against i.p. L1210 leukemia. However, in terms of molar doses resulting in the death of 10% of normal mice, the cis- and trans-2 isomers were 2- and 3-fold more toxic than was CCNU in normal mice. In comparing the antitumor activity produced by a maximum nonlethal dose for each compound, we found that the trans isomer had activity identical to that of CCNU (413 and 410% increased life span compared to control), and the cis isomer had considerably less (152%). Like chlorozotocin, both isomers possess low carbamoylating activity and increased water solubility, two features that have been considered possible contributors to the bone marrow-sparing character of chlorozotocin. However, in the murine model the human bone marrow colony formation (CFU-C) assay neither hydroxylated metabolite of CCNU was associated with reduced myelotoxicity.
Cancer Res 1978 Apr
PMID:Biological and biochemical properties of the 2-hydroxyl metabolites of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. 14 30


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