PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “carcinogenesis”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1978

[Co-carcinogens or modulators of carcinogenesis. New aspects of the etiology of human tumors and of the molecular mechanisms of carcinogenesis].

Within the last 10 years numerous new and typical exogenous cocarcinogens were identified chemically as well as biologically and characterized biochemically as initiation or tumor promoters. They are highly irritant diterpene esters of plant origin. Promoters of this type were recently detected also in the Euphorbiacea Croton flavens L., the multiple use of which for stimulants according to local habits was previously held responsible for the unusually high rate of esophageal cancer on Curacao. This detection confirms for the first time that in the etiology of human cancer besides solitary carcinogens (first-order carcinogenic risk factors) also cocarcinogens of the promoter type have to be considered (second-order carcinogenic risk factors). -- The active principles of the diterpene ester type are the strongest promoters known so far; they are noninitiators and nonmutagens. Of the manyfold biochemical activities of these promoters the three most actual are: the TPA molecule does not require activation by metabolic alteration, it releases very rapidly prostaglandin E2 from cellular membranes and it activates latent DNA-viral genoms.

Animals↗
PubMed1978

Experimental pancreatic carcinogenesis. II. Lifetime carcinogenesis studies in the outbred Syrian golden hamster with N-nitroso-bis(2-hydroxypropyl)amine.

A high incidence of pancreatic duct neoplasms was induced in outbred male Syrian golden hamsters following weekly sc injection of N-nitroso-bis(2-hydroxypropyl)amine for life. The first such tumors appeared as early as 16 experimental weeks; the maximum incidence reached 100% by the termination of the study. Tumors in the respiratory tracts and angiosarcomas of the livers of the hamsters were also observed in high frequency. Latency of the induced neoplasms was significantly decreased by the substitution of distilled water for olive oil as the vehicle for the carcinogen.

Animals↗
PubMedDate not supplied

Pancreatic carcinogenesis and naturally occurring pancreatic neoplasms of rats and mice in the NCI carcinogenesis testing program.

Over two hundred chemicals were examined in a two year rodent bioassay system for possible carcinogenicity. Of these, only nitrofen significantly increased the incidence of neoplasms of the exocrine pancreas of rats or mice (female Osborne-Mendel rats); azinphosmethyl was the only agent tested which significantly increased the incidence of islet-cell tumors of rats or mice (male Osborne-Mendel rats). The use of the rat (Osborne-Mendel or Fischer 344) and mouse (B6C3F1) as models for the detection of chemically-induced pancreatic neoplasms also was investigated. The incidences of specific neoplasms of the exocrine or endocrine pancreas produced by all chemicals tested were combined and compared with the combined incidences of similar neoplasms in control animals in order to increase the sensitivity of the test. The data obtained through this procedure suggests that the male rat may be a good, sensitive model for the detection of islet-cell tumors.

Animals↗
PubMed1977

Mutational approaches to the study of carcinogenesis.

A number of circumstantial lines of evidence are consistent with the somatic mutation theory of carcinogenesis, but there has been a paucity of experimental data that either support or contradict the genetic theory. In this paper, we summarize the predictions, the recent experimental approaches, and the problems involved in testing the theory. Results are presented that define the conditions and demonstrate the existence of two-stage processes of mutagenesis and carcinogenesis in vitro. We conclude that mutagenesis is responsible for the initiation of carcinogenesis and an epigenetic mechanism is responsible for its promotion. Carcinogenic agents can induce a stable transformation of a cell by either mutation or epigenetic alteration in gene expression. This conclusion has led us to propose a new integrative theory of carcinogenesis, encompassing the tenets of four main theories: (1) the mutation and epigenetic basis for carcinogenesis, (2) the two-stage theory of carcinogenesis, (3) a general theory of carcinogenesis, and (4) the somatic deletion mutation theory of carcinogenesis.

Animals↗
PubMed1978

Environmental carcinogenesis: an integrative model.

An integrative theory is proposed in which environmental carcinogenesis is viewed as a process by which the genetic control of cell division and differentiation is altered by carcinogens. In this theory, carcinogens include physical, chemical, and viral "mutagens," as well as chemical and viral gene modulators. Existing explanations of carcinogenesis can be considered either as somatic mutation theories or as epigenetic theories. Evidence seems to support the hypothesis that both mutations and epigenetic processes are components of carcinogenesis. The mutational basis of cancer is supported by the clonal nature of tumors, the mutagenicity of most carcinogens, high mutation frequencies in cells of cancer-prone human fibroblasts lacking DNA repair enzymes, the correlation of in vitro DNA damage and in vitro mutation and transformation frequencies with in vivo tumorigenesis, age-related incidences of various hereditary tumors, and the correlation between photoreactivation of DNA damage and the biological amelioration of UV-induced neoplasms. Since both mutagens and gene modulators can be carcinogenic it may be that carcinogens affect genes which control cell division. An integration of the mutation and epigenetic theories of cancer with the "two-stage" theory and Comings's general theory of carcinogenesis is proposed. This integrative theory postulates that carcinogens can affect regulatory genes which control a series of "transforming genes." A general hypothesis is advanced that involves a common mechanism of somatic mutagenesis via error-prone repair of DNA damage which links carcinogenesis, teratogenesis, atherosclerosis and aging. Various concepts are presented to provide a framework for evaluating the scientific, medical, and social implications of cancer.

Aging↗
PubMed1978

Carcinogenesis induced by 7,12-dimethylbenz[a]anthracene in c3H-A vyfB mice: influence of different dietary fats.

The effect of a diet containing either sunflower-seed oil (polyunsaturated fat diet) or tallow (saturated fat diet) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis in C3H-A vyfB mice was examined. After receiving either diet for 28 days, some of the mice were given an intragastric dose of 5 mg DMBA. To identify the stage of carcinogenesis that might be influenced by dietary fat, the diets of half of the mice were then interchanged so that those previously fed the saturated fat diet were fed the polyunsaturated fat diet and vice versa. The cumulative incidence of tumor-bearing mice was significantly greater among the females fed the polyunsaturated fat diet compared to those fed the saturated fat diet. This enhancement of carcinogenesis was observed only when the mice were fed the polyunsaturated fat diet after DMBA administration. Similar trends were observed in the male mice, but these mice developed fewer tumors and none of the differences between the tumor incidences were statistically significant. The most common sites for tumors in the male mice were the liver, lungs, and skin, whereas those for tumors in the females were the mammary glands and ovaries. The differences in tumor incidence suggest that carcinogenesis was enhanced by the polyunsaturated fat diet during the promotion stage of carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Neoplastic response of mouse tissues during perinatal age periods and its significance in chemical carcinogenesis.

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.

Animals↗
PubMed1979

[Molecular aspects of carcinogenesis (author's transl)].

The mechanism of carcinogenesis is not yet understood. There is increasing evidence justifying the assumption that an unifying concept of carcinogenesis should be possible at the molecular level. New insights into the molecular mechanism of carcinogenesis were mainly obtained in studies on both chemical and viral carcinogenesis. In the present paper, selected results of these studies are reviewed. It is concluded that the interaction of different carcinogenic agents with the cellular DNA results in alterations of DNA. Only some of these alterations, however, seem to be relevant to carcinogenesis. Alterations of DNA can be caused by reaction of electrophilic agents with DNA constituents, by increased infidelity of DNA replication, by integration of viral genomes or by recombination events involving integrated proviruses.

Carcinogens↗
PubMed2026

Temporal Transcriptomic Profiling of NMBA-Induced Rat Esophageal Squamous Carcinogenesis Identifies Early Inflammatory Activation and Late NRF2-Associated Oxidative-Stress Remodeling.

Temporal molecular events during early esophageal squamous carcinogenesis remain incompletely defined, in part because human precursor tissues are difficult to obtain sequentially. We used the N-nitrosomethylbenzylamine (NMBA)-induced rat model to characterize stage-associated transcriptional programs during esophageal squamous carcinogenesis. Vehicle-control reference esophageal tissues and NMBA-treated esophageal tissues, collected at weeks 6 and 29, were profiled using Affymetrix Rat Genome 230 2.0 arrays, followed by pathway analysis and qRT-PCR validation of selected genes. Relative to vehicle-control reference tissues, 173 genes were differentially expressed at week 6, whereas 1628 genes were differentially expressed at week 29, indicating marked expansion of transcriptional dysregulation during carcinogenic progression. Sixteen genes were differentially expressed only at week 6, while 157 genes were altered at both time points. Pathway analysis suggested that inflammatory and immunologic processes were prominent during the early response to NMBA exposure, whereas late-stage carcinogenesis was characterized by NRF2-associated oxidative-stress response and dysregulation of multiple glutathione S-transferase family members. A subset of progression-associated genes, including Defb4, Gsta2, Sbsn, Spink5, Plcd4, Hbb, and Hba-a2, showed increasing dysregulation from week 6 to week 29. These findings define temporally distinct molecular programs in NMBA-induced esophageal squamous carcinogenesis and provide a framework for prioritizing candidate pathways and genes relevant to esophageal cancer prevention, early detection, and progression biology.

Animals↗
PubMed1979

Effects of progesterone on mammary carcinogenesis by DMBA applied directly to rat mammae.

The effects and site(s) of action of progesterone on DMBA mammary carcinogenesis in the rat, when a small dose of the carcinogen was applied directly to the inguinal mammary gland, were investigated. No reduction in tumour yield was apparent when progesterone was administered s.c. for 18 days before dusting DMBA. This finding contrasts with a previously reported inhibitory effect on carcinogenesis when hormone treatment was followed by intragastric administration of DMBA. When progesterone injections were begun either 2 days before or 2 days after direct application of DMBA, and were continued until the end of the experiment (135 or 195 days) an enhancement in carcinogenesis was observed similar to that previously demonstrated after gastric intubation of DMBA. These findings, together with previously reported observations, suggest that progesterone may exert its inhibitory effect on carcinogenesis by acting at a site outside the breast, perhaps on the liver. However, it is likely that the hormone acts directly on the mammary tissue to exert its enhancing effect on tumorigenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Effect of Salmonella enteritidis 11RX infection on two-stage skin carcinogenesis in mice.

S. enteritidis 11RX infection inhibits the growth of a number of transplantable tumours in mice. In addition, oral infection of mice with S. enteritidis 11RX inhibits colon carcinogenesis by 1,2 dimethylhydrazine. This study has examined the effect of S. enteritidis 11RX infection on two-stage skin carcinogenesis in mice using 7,12 dimethylbenz(a)anthracene (DMBA) as initiator and croton oil as promoter. No protection was observed in either LACA or (BALB/c x C57Bl/6J)F1 mice when live 11RX was repeatedly administered i.v. during promotion. When a protein antigen extract from S. enteritidis 11RX was administered i.v. to previously immunised mice during skin carcinogenesis, significant protection was observed both in terms of the number of mice with papillomas and the number of papillomas per mouse. However, the protection was weak and transient. LACA mice were much more susceptible to skin carcinogenesis by DMBA and croton oil than were (BALB/c x C57B1/6J)F1 mice. A preliminary study indicated that BALB/c, C57B1 and CBA mice were also relatively resistant to skin carcinogensis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Effects of essential amino acid deficiencies on syngeneic tumor immunity and carcinogenesis in mice.

The present study was designed to evaluate in a syngeneic system the longterm effect of dietary reduction of each of three essential amino acids on carcinogenesis with methylcholanthrene (MCA) and immunity to a transplanted MCA tumor. Inbred mice were provided a standard amino acid diet or a diet deficient in isoleucine, leucine, or phenylalanine-tyrosine. In the carcinogenesis experiment, MCA pellets were implanted in each mouse and weekly records were maintained of body weight, tumor incidence, tumor size, and death rate. Mice in the immunity study were inoculated with syngeneic tumor cells; tumors were excised when the largest tumor in the control group reached 12 mm and each animal then received a second challenge of tumor cells. The available data suggest that (1) restriction of the selected amino acids does not inhibit chemical carcinogenesis with MCA, (2) phenylalanine-tyrosine deficiency may actually enhance chemical carcinogenesis with MCA, and (3) selected essential amino acid deficiencies do not enhance immunity to a transplanted MCA tumor.

Amino Acids, Essential↗
PubMed1976

Cutaneous chemical carcinogenesis: past, present, and future.

Skin tumors chemically induced in mice have provided an important experimental model for studying carcinogenesis and for bioassaying carcinogenic agents. The information obtained from this model suggests that the events leading to tumor formation can be divided into at least two stages, initiation and promotion. A single small dose of carinogen produces initiation which appears to be irreversible. These initiating agents may have to be metabolically activated and can interact with cellular macromolecules. The extent to which they bind to DNA correlates well with their carcinogenicity. Increased DNA replication at the time of or during the first day after these agents have been applied appears to enhance carcinogenesis. Unlike initiation, promotion appears to be reversible and the promoting agents must be applied repeatedly before tumors are formed. Promoters interact with membranes, stimulate and alter genetic expression, and increase the rate of cell proliferation. The knowledge gained from these studies in mouse skin has immeasurably helped the entire field of chemical carcinogenesis. But efforts to determine the cellular and molecular mechanisms involved in the carcinogenic process, particularly in the skin, have been hampered by the difficulties of working on whole animals and by the special problems associated with the biologic and biochemical methods required for this target organ. Such problems, however, can be solved by the use of cell cultures of mouse epidermis which can metabolize and bind carcinogens just as is done in vivo. The fact that epidermal cells in vitro proliferate synchronously should facilitate the study of the relation between the cell cycle and carcinogenesis. These cells repair chemically induced DNA damage by at least two mechanisms, excision repair and base-specific repair. When epidermal cells in vitro are exposed to promoting agents, a proliferative response analogous to that in vivo is elicited, apparently mediated through control of polyamine metabolism. Neoplastic transformation has been induced in these cultures by known skin carcinogens.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Influence of surface lipids on skin carcinogenesis in rats.

Skin tumours were indeuced in female Wistar SPF-rats by different polycyclic aromatic hydrocarbons, benzo[alpha]pyrene (BP), dibenz[alpha, h]anthracene (DBA), 7,12-dimethylbenz]alpha]anthracene (DMBA), and 3-methylcholanthrene (MCA) being applied on the dorsal skin of 20 rats each. DBA was not carcinogenic under the experimental conditions. DMBA proved the most potent carcinogen, and MCA was more potent than BP. Half of the animals in each group underwent skin-surface lipid extraction (SSLE) before the application of carcinogen. SSLE did not influence the cumulative number of rats with skin tumours during an observation period of 15 months nor the type of tumours induced. The lipid extraction, however, increased the latency period and decreased the rate of tumour development when BP and MCA acted as carcinogens. On the contrary, SSLE enhanced the rate of tumour production by DMBA and reduced the latency period. The role of sebum and its composition in skin carcinogenesis is discussed, and an explanation of the different influence of SSLE on BP and MCA carcinogenesis is discussed, and and explanation of the different influence of SSLE on BP and MCA carcinogenesis in contrast to DMBA carcinogenesis is sought in differences in metabolic activation of the carcinogens.

9,10-Dimethyl-1,2-benzanthracene↗