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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously studied some parameters of rat liver activity and compared the kinetics of cell proliferation (normal growth or after partial hepatectomy) with some specific hepatic enzymes. The mutually exclusive relationship between division and tissue function, their specific circadian rhythm as well as the "chalone effect" have been used to characterize the normal homeostatic regulatory mechanism in the liver. The same parameters have been recently determined during chemical carcinogenesis. Adult rats, fed long term with diethylnitrosamine (DENA, 10 mg/kg/day) develop liver carcinoma after 90 days of carcinogen administration. The results show that the relationship between the above parameters is progressively disturbed during the second month of treatment. A minimum of 4 weeks of continuous DENA feeding is found to be necessary for the induction of liver cancers. Giving the carcinogen for a second month decreases the delay before death with cancer. Protracting the treatment after the second month has no further effect either on survival or on cancer induction. The mechanism of carcinogenesis is explained by postulating that preneoplastic lesions evolution would closely depend on the homeostatic control disturbances.
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PMID:Correlation of liver growth and function during liver regeneration and hepatocarcinogenesis. 15 18

A series of studies pertaining to perinatal carcinogenesis have been reviewed. Their main objective was development and definition of a sensitivity biologic model for carcinogenicity screening. Data were summarized on factors modifying the carcinogenic response of various tissues following transplacental, neonatal-infant, or adult exposure of (B57BL/6J X C3HeB/FeJ)F1 mice to a single administration of ENU. In addition, tumor response of mice treated during specific perinatal age periods with DEN, BP, aflatoxin B1, benzidine . 2HCl, DDT, dieldrin, and safrole were analyzed. The results revealed that the age of the animals at the time of carcinogenic exposure has been the most effective modulator of carcinogenesis in liver, lung, stomach, ovary, and lymphoreticular tissues. Infancy proved to be the most susceptible period to carcinogenesis as demonstrated by a great variety of tissues that responded to treatment and the incidence of tumors which developed. Depending on the nature of carcinogen, variation in organ sites undergoing carcinogenesis was considerable, apparently due to difference in their enzymatic competence to activate and metabolize the agent. Thus a single treatment with ENU, a spontaneously activated type of procarcinogen, induced 59 primary types of tumors in 22 tissues. In contrast, treatment of infants by procarcinogens requiring enzymatic activation led to development of tumors only at a limited number of tissue sites. However, regardless of the type of carcinogen used, the liver consistently responded with development of tumors. Detailed morphologic and biologic evaluations of the induced liver tumors demonstrated in addition to the benign neoplastic variety, the presence of the frank malignant tumors. The character of tumors was dependent not only on carcinogenicity of the agent used but also on the age of mice at the time of carcinogenic treatment. Perinatally induced primary liver tumors showed greater tendency to metastasize and were more readily transplantable into an isogeneic host than those induced at later age periods. Data showed the advantage of prenatal and/or postnatal treatment in combination of life-long exposures to test agents as a more sensitive bioassay system in comparison with solely postweaning treatment. Because the early age period is the most sensitivity life phase to carcinogenesis, it appears to be a good model for prescreening various potential carcinogens, especially when only small amounts of test substances are available. The importance of the proper relationship of such bioassay to the other test systems regarding assessment of potential human risk has been emphasized.
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PMID:Neoplastic response of mouse tissues during perinatal age periods and its significance in chemical carcinogenesis. 38 63

The significance of tissue differentiation for the transplacental carcinogenicity of DEN was examined. In one experiment, pregnant Syrian golden hamsters received a single sc injection of DEN on one of the different days of pregnancy. Approximately 95% of the offspring of those mothers treated on one of the last 4 days (days 12--15) of gestation developed respiratory tract tumors. Transplacental DEN treatment before the 12th prenatal day failed to induce any neoplastic response in the young. In the second experiment, the differentiation of the prenatal Syrian golden hamster tracheal epithelium was examined histologically and by electron microscopy. We found that on the 12th prenatal day the ER occurred for the first time in its functionally competent form. On earlier prenatal days, the epithelial cells lacked this organelle. We conclude that this development of ER is a prerequisite for transplacental DEN carcinogenesis, since this organelle contains the nonspecific enzyme systems necessary for the transformation of DEN to its ultimate carcinogen.
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PMID:Tissue differentiation as a prerequisite for transplacental carcinogenesis in the hamster respiratory system, with specific respect to the trachea. 48 73

There were found certain changes in the total content of phospholipids as well as in the content of their separate fractions in the membranes of endoplasmic reticulum in the rat liver at early stages of carcinogenesis. In the first week under the carcinogen DENA exposure a considerable reduction of the total phospholipids content was noted in the fraction of granular endoplasmic reticulum, while in agranular reticulum during this period of embryogenesis the total content of phospholipids is not changed, but subsequently the former increases as compared with normal values. During the whole period of carcinogenesis under study changes in the phospholipid content are observed in both fractions of endoplasmic reticulum membranes, the greatest changes being noted in the fractions of lysophosphatidicholines, phosphatidilcholines, and phosphatidilinosites.
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PMID:[Membrane phospholipids of the rat liver endoplasmic reticulum normally and in the early stage of carcinogenesis]. 71 16

Experimental models have been developed for the induction of carcinoma of the larynx and for the study of its pathogenesis. The hamster has been the animal of choice. Polynuclear hydrocarbons, administered intratracheally, induce mostly squamous cell carcinomas. Diethylnitrosamine given systemically induces papillary tumors; some other N-nitroso-compounds given topically or systemically also induce laryngeal tumors, including carcinomas. Cigarette smoke inhalation induces preneoplastic and early neoplastic lesions of the larynx, including some invasive carcinomas. In vivo and in vitro methods have been developed for the morphological and biochemical study of target tissues in respiratory epithelial carcinogenesis to identify critical pathogenetic steps and their inhibition. These methods are now applicable to the in vitro study of human laryngeal epithelium and its susceptibility to cancer induction and prevention.
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PMID:Carcinogenesis of laryngeal carcinoma. 109 93

The tumor-promoting and carcinogenic effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) in the liver and in other organs were quantified and compared to those of phenobarbital (PB) in two inbred strains of mice (C57BL/6NCr, DBA/2NCr) and in F344/NCr rats initiated at 5 weeks of age with N-nitrosodiethylamine (NDEA; 90 mg/kg in mice, 75 mg/kg in rats). Two weeks later animals were placed on a regimen of TCPOBOP once every 2 weeks (administered i.p. or i.g.) or on a diet containing 500 p.p.m. PB as a positive control for the duration of the experiment. Mice were administered TCPOBOP (3.0 mg/kg/dose) for 30 weeks followed by control diet, while rats were given the TCPOBOP regimen (3.0 or 30 mg/kg/dose) for the full 78 weeks of the experiment. TCPOBOP was a complete carcinogen and an extremely potent promoter in both strains of mice, particularly the DBA strain in which NDEA followed by TCPOBOP (i.p.) resulted in death of all the animals within 30 weeks from multiple hepatocellular tumors. TCPOBOP alone induced 100% tumor incidence in DBA mice within 60 weeks. In addition, in both strains of mice, a high proportion of those animals with liver tumors had metastases to the lungs. In contrast, TCPOBOP was ineffective as a liver tumor promoter in F344 rats at even 10 times the dose administered to mice. Interestingly however, TCPOBOP, when given subsequent to NDEA, caused a significant increase in nasal cavity tumors in F344 rats. PB was an effective liver tumor promoter in male DBA mice and male F344 rats, but was relatively ineffective as a promoter in C57 mice. When tumor-promoting activity and induction of cytochrome P450 IIB1 were compared, good agreement between these two parameters was observed. PB was an effective inducer of P450 IIB1 in the rats and in both strains of mice and a potent liver tumor promoter in both DBA mice and F344 rats, whereas TCPOBOP was a potent inducer and tumor promoter in both strains of mice but was negligibly effective as either an inducer or a promoter in F344 rats at even 10-fold higher dosage.
Carcinogenesis 1992 Oct
PMID:Tumor-promoting and hepatocarcinogenic effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) in DBA/2NCr and C57BL/6NCr mice and an apparent promoting effect on nasal cavity tumors but not on hepatocellular tumors in F344/NCr rats initiated with N-nitrosodiethylamine. 133 Mar 46

Previous studies have suggested that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) acts as a promoting agent in various organ systems including the rat liver. Since a major characteristic of the stage of tumor promotion is its operational reversibility, we have assessed whether TCDD-induced promotion is reversible in a two-stage model of hepatocarcinogenesis. In this model, female Fischer F344 rats were administered a single, intragastric dose of the initiating agent, diethylnitrosamine (DEN, 10 mg/kg), at the peak of proliferation induced by a partial hepatectomy. TCDD was then administered biweekly (0.14 micrograms/kg, s.c.) for 1, 3 or 5 months. One group of animals was killed at each of these time points, while a second group was maintained for each time point for an additional 6 months in the absence of further TCDD. Four serial frozen sections of liver were each stained with a different enzyme marker of altered hepatic foci (AHF). The AHF were identified and the number and volume fraction determined by quantitative stereology. Exposure to TCDD resulted in an increase in the number and size of AHF in the initiated relative to the uninitiated rats. Increasing the duration of promotion with TCDD led to an increase in the number of AHF per liver, the volume fraction of the liver occupied by AHF and the number of markers expressed aberrantly by a single AHF. Discontinuation of TCDD administration for 6 months before killing the animals resulted in a decrease in the total number of AHF observed, but those AHF that remained increased in size with an overall increase in volume fraction of AHF. Analysis of the size class distribution for AHF for each of the periods of TCDD promotion revealed an increase in the larger AHF but a decrease in the smaller, thereby resulting in an overall decrease in number of AHF with an increase in the volume fraction of AHF. Increasing the duration of the TCDD exposure prior to its withdrawal led to an increased AHF size, phenotypic complexity and number of AHF remaining after cessation of TCDD administration. Although the levels of TCDD in livers of rats 6 months after cessation of TCDD administration were still greater than background, they were markedly reduced compared to immediately after administration. Thus, cessation of exposure to TCDD after a brief duration led to a reversal of its promotional effects on the majority of AHF, while prolonged exposure led to maintained promotion of a minority of AHF.
Carcinogenesis 1992 Aug
PMID:Characterization of the promotion of altered hepatic foci by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the female rat. 135 83

Diethylnitrosamine (DEN) and methylazoxymethanol acetate (MAM) are not transplacental carcinogenic but embryotoxic to Wistar rats when administered by i.p. injection on day 12 of gestation. MAM, a weak teratogen to rats during this period, induced a dose dependent increase in the number of resorptions to 15% and 40% of the litters following doses of 15 and 25 mg/kg bw, respectively. Rats similarly treated with 70, 150, and 180 mg DEN/kg bw resulted in increases in total DNA mass of day 13 embryos by 31%, 45% and 52%, respectively, compared to the saline treated controls. Twenty percent reduction in total DNA amount was detected following 25 mg MAM/kg bw. Benzoylated DEAE-cellulose (BD-cellulose) chromatography fractionates DNA on the basis of secondary structure by stepwise elution of double-stranded DNA with 1.0M NaCl solution (SE-DNA) followed by elution of DNA containing single-stranded regions with caffeine solution (CE-DNA). Day 13 embryonic DNA was monitored by in vivo labelling with [methyl-3H]-thymidine (3H-TdR) on days 6 and 7 of gestation. Significant increases in percentages of caffeine-eluted DNA (%CE-DNA) compared to control values were detected 24 h after treatment of day 12 embryos with 70, 150, and 180 mg DEN/kg bw. Such increases were not observed after MAM. Incorporation of [methyl-14C]-thymidine (14C-TdR) into embryonic DNA demonstrated the effects of treatment with these compounds on DNA synthesis in vivo. When compared to saline controls, DEN induced significant increases in 14C-TdR incorporation into embryo DNA, 1 h prior to analysis, but the increases were not proportional to the doses administered. Similar analysis of MAM treated samples showed no significant changes to %CE-DNA values. The relative %CE-DNA is expressed as the ratio of the percentage of caffeine-eluted 14C-labelled DNA to %CE-DNA (i.e., %CE-14C-DNA:%CE-3H-DNA). In the majority of control embryos the 14C-specific activity of CE-DNA was higher than the 14C-specific activity of SE-DNA. No significant change to relative %CE-DNA values of embryos to those of the controls was observed 24 h after treatment of day 12 gestation rats with single doses of DEN and MAM. The results of this study support the hypothesis that initiation mechanisms of teratogenesis and transplacental carcinogenesis are different. The pertinence of %CE-DNA and relative %CE-DNA values to teratogenesis and transplacental carcinogenesis is also discussed.
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PMID:Changes in secondary structure of DNA of rat embryos following treatment with diethylnitrosamine and methylazoxymethanol acetate in vivo. 136 96

The Chemoprevention Branch is testing dozens of candidate chemopreventive compounds in the following rodent model carcinogenesis systems: mouse skin papillomas, DMBA/TPA induced, rat mammary adenocarcinoma, DMBA and MNU induced, hamster tracheal squamous cell carcinoma, MNU induced, and lung adenocarcinoma, DEN induced, rat and mouse colon adenocarcinoma, AOM and MAM acetate induced, respectively, and mouse bladder carcinoma, hydroxy BBN induced. Significant chemopreventive (i.e., anticancer) effects have been produced with 4-hydroxy-phenylretinamide, difluoromethylornithine, piroxicam, oltipraz (a dithiolthione), calcium glucarate, N-acetylcysteine, beta-carotene, ibuprofen, dehydroepiandrosterone (DHEA) and a 16-fluoro DHEA analog, 8354, tamoxifen, glycyrrhetinic acid, molybdate, selenite, curcumin, and fumaric acid.
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PMID:Screening for chemopreventive (anticarcinogenic) compounds in rodents. 137 27

The progression of hepatocellular adenomas to carcinomas has been less well documented in mice than in rats. We studied progression of spontaneous and chemically induced hepatocellular adenomas in male C3H/HeNCr mice by image analysis. Spontaneous lesions in 15, 18 and 21 month old untreated male C3H/HeNCr mice and experimentally induced lesions were examined. Experimental group 1 received a single i.p. injection of N-nitrosodiethylamine (DEN) (5 mg/kg body wt) at 15 days of age. Groups 2 and 3 were injected a second time with DEN at 15 or 20 weeks of age (75 mg/kg body wt), with interim sacrifices at 11, 16 and 34 weeks after the second DEN injection. Atypia in adenomas were classified into four grades according to cell size, tinctorial changes, cellular pleomorphism and trabecular pattern. At earlier stages of the neoplastic process (11 or 16 weeks after the second DEN dose), most adenomas were well-differentiated lesions with no atypia or focal grade 1 or 2 atypia. At later stages (34 weeks after the second DEN dose), a large proportion of hepatocellular tumors were classified as adenoma with grade 3 atypia or carcinoma. The proportion of carcinomas in mice treated with a second dose of DEN at 20 weeks of age was significantly higher than in mice treated with a single dose of DEN or in mice given a second dose of DEN at 15 weeks. A positive correlation was found between increase in the size of lesions and increased atypia in both spontaneous and DEN-induced lesions and with age for spontaneous tumors. These results support the hypothesis that mouse hepatocellular adenomas are truly neoplastic lesions in different stages of progression toward malignancy.
Carcinogenesis 1992 Sep
PMID:Progressive atypia in spontaneous and N-nitrosodiethylamine-induced hepatocellular adenomas of C3H/HeNCr mice. 139 37


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