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

Keratinocytes from mouse skin were cultured for a short period in vitro following single or multiple treatments at low dose levels in vivo with the known chromosome-damaging agent triethylenemelamine (TEM). The chemical was applied to the skin of HRA/Skh hairless mice at concentrations corresponding to those reported to initiate cancer in initiation-promotion assays. A significant dose-related depression in keratinocyte cell recovery occurred over the dose range 0.3-1 mg TEM/mouse (single or multiple treatments). Under the same conditions, a dose-related induction of micronuclei was observed using the cytokinesis-block method with cytochalasin B. A similar frequency of micronuclei was detected in binucleate cells from mice treated with single or multiple applications of TEM. Mice held for 12-48 h post-treatment, before removal of skin for in vitro culture, yielded highest micronuclei frequencies. These results indicate that the same target cell population, skin keratinocytes, can be used to investigate both genotoxicity and carcinogenesis, and that micronucleus induction in these cells may be a sensitive signal of skin cancer initiation.
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PMID:Initiating carcinogen, triethylenemelamine, induces micronuclei in skin target cells. 275 23

Oral retinoid therapy has been considered for the prevention of skin carcinogenesis in humans, although animal studies have failed to provide any evidence of a protective effect of these drugs in the one-step photocarcinogenic system. In this study, oral therapy with vitamin A or a synthetic analogue, etretinate, was tested for ability to protect hairless mice (Skh-hr1) from the development of skin tumours following exposure to broad-band light (280-700 nm) for 25 weeks. Retinoids were given by gavage 3 times weekly either at low dosage (2000 IU vitamin A or 4 mg etretinate per kg body weight) or high dosage (10,000 IU vitamin A or 20 mg etretinate per kg body weight). None of the retinoid therapies compared to control mice (gavage vehicle only) modified skin tumour production in terms of time to onset of tumours, total tumour yield, or the types of tumours produced.
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PMID:Effects of oral retinoid (vitamin A and etretinate) therapy on photocarcinogenesis in hairless mice. 278 Aug 16

Different opinions exist on the normal ultrastructure of the epidermis including the significance of so-called basal dark cells. Thus, the dark cells are still assumed to be key elements in experimental skin carcinogenesis. We therefore explored the effects of tissue fixation on the ultrastructure of the epidermis. Untreated normal hairless mouse skin was processed for transmission electron microscopy with two different sets of fixatives, applied either by perfusion-immersion or immersion fixation only. The morphology of both the basal and the lower suprabasal layers of the epidermis, including the extracellular space, the shape and volume of the cells, their electron density, and the organisation of some of the organelles, were profoundly affected by the choice of fixatives. The non-keratinocytes showed comparable changes, including the appearance of a dark phenotype. The incidence of small electron-dense keratinocytes (dark cells) and the nature of their ultrastructure changed markedly with the fixation procedure. We were not able to identify undifferentiated dark cells. The pattern of changes and the quality of the morphological picture were almost unaffected by the mode of fixation. The upper suprabasal and the cornified layers appeared to be more or less unaltered by the change in fixatives and the method of application. The vehicle osmolality of the primary fixative was found to be mainly responsible for the ultrastructural appearances. A low vehicle osmolality may be responsible for the occurrence of the dark cell phenomenon, by inducing swelling artefacts of many cells with compression of some neighbouring cells.
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PMID:The influence of fixation on the morphology of mouse epidermis. A light and electron microscopical study with special reference to "dark cells" and epidermal carcinogenesis. 289 10

Several groups of hairless mice were given UV radiation with and without pretreatment with 7,12-dimethylbenz(a)anthracene (DMBA), 5% benzoyl peroxide in a gel (Panoxyl), and gel alone, in various combinations, with appropriate control groups included, in order to see whether benzoyl peroxide, which is known to enhance chemical skin carcinogenesis after a single, small dose of DMBA, also enhances UV carcinogenesis. The mice were observed for skin tumors, and all skin lesions were histologically investigated. The percentage of tumor-bearing animals with time is called the tumor rate, the total number of tumors occurring is called the tumor yield. Continual treatment with 5% benzoyl peroxide in gel twice a week, with or without a short pretreatment period of UV radiation resulted in only 2 skin carcinomas, which is remarkable, but not significant. Both Panoxyl and gel alone enhanced tumorigenicity significantly in animals pretreated with a single dose of 51.2 micrograms DMBA. There was no difference between the enhancement caused by Panoxyl and the gel as regards the tumor rate, but when measured as final tumor yield, Panoxyl was slightly more tumor-enhancing than gel alone. However, both Panoxyl and gel protected significantly against UV tumorigenesis (all tumors). There was no difference between the protective effect of the 2 types of treatment. Neither Panoxyl nor gel alone influenced significantly UV skin carcinogenesis (malignant tumors). It is concluded that under these experimental conditions both Panoxyl and gel alone tend to protect against the tumorigenicity and do not enhance the carcinogenicity of UV radiation in hairless mice, whereas both gel and Panoxyl enhance chemical carcinogenesis. The carcinogenic mechanisms may be different for UV and chemical carcinogenesis, respectively.
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PMID:Carcinogenesis studies with benzoyl peroxide (Panoxyl gel 5%). 309 6

To study whether fluorescent lighting at work might increase carcinogenesis, hairless mice were exposed to a bank of six 36 W standard fluorescent lamps (neutral-white) every workday for 8 h at an illuminance level of 1,000 lx. For comparison, other mice were exposed to UVB radiation or to simulated solar radiation. In experiment A the animals were irradiated for 6 weeks prior to the application of 7,12-dimethyl-benzanthracene once and--following an interval of 2 days--for 10 weeks after DMBA application. The number of blue nevi and papillomas was enhanced by exposure to all spectra 10 weeks after chemical tumor induction. In experiment B the animals were irradiated for 6 weeks prior to the transplantation of UV-induced fibrosarcoma cells from syngeneic mice into the dorsal and ventral skin. Within the following 4 months fibrosarcoma developed in the dorsal skin exposed to the fluorescent lighting and to the UVB radiation, as well as in the non-irradiated ventral skin of 10-20% of the mice. The results suggest that fluorescent lighting as used in certain work environments may increase carcinogenesis caused by other factors.
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PMID:Fluorescent lighting enhances chemically induced papilloma formation and increases susceptibility to tumor challenge in mice. 309 30

Groups of hairless (hr/hr) mice were given a single, topical skin application of either 50, 5 or 0.5 micrograms 7,12-dimethylbenz[a]anthracene (DMBA). At different times up to 3 days after treatment epidermal DNA distribution patterns were determined by flow cytometry, and sp. act. of DNA and labeling indices were obtained based on incorporation of [3H]thymidine. Mitotic rates were determined by the Colcemid method, and the number of basal and suprabasal cells were scored in histological sections. All three doses of DMBA led to an early depression in the uptake of [3H] thymidine, associated with an accumulation of cells with S phase DNA content peaking at 16 h. By combining the methods for studying DNA synthesis, it can be concluded that the alterations observed probably were due to a slow rate of DNA synthesis in the S phase cells, rather than to a block at the entrance of cells into the S phase. Three days after the application, DMBA still maintained an effect on the cell cycle progression, at least in the S phase. There was an obvious dose-response relationship in the inhibition of epidermal DNA synthesis. Six hours after application of the two highest doses of DMBA an early increase in the mitotic rate was observed. This short-lasting high mitotic rate was followed by a transient, very brief increase in the number of suprabasal cells. Thereafter a decrease in both the mitotic rate and the number of suprabasal cells occurred, probably caused by the alterations in DNA synthesis. After the lowest dose there was no such early increase in the mitotic rate and no initial, short-lasting increase in the number of suprabasal cells. Hence, this study shows that decreasing doses of DMBA provoke decreasing degrees of the same type of cell kinetic perturbations in the epidermal cell cycle.
Carcinogenesis 1987 Oct
PMID:Cell kinetic effects of low doses of the skin carcinogen 7,12-dimethylbenz[a]anthracene on hairless mouse epidermis. 311 12

In a previous paper it was demonstrated on hairless mouse skin that 5% benzoyl peroxide (BP) in a gel (Panoxyl), or gel alone, applied just before UV radiation had a protective effect against UV-induced tumorigenesis, but both enhanced 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumorigenesis. Groups of hairless (hr/hr) mice were therefore given ultraviolet (UV) irradiation with or without additional treatment with Panoxyl or gel in order to see whether Panoxyl or the gel given long time before, or after, irradiation influenced UV-induced tumorigenesis. Consequently, in some animals Panoxyl or gel was applied in the evening and the mice were irradiated the next day; in others, Panoxyl or gel was applied 5-30 min after UV irradiation. Enhancement of DMBA-induced carcinogenesis in hr/hr mice by the gel alone (assumed to be inert) was unexpected, and hence one group of hr/hr mice was first given 51.2 micrograms DMBA in acetone and thereafter treated twice a week with gel alone. All mice were tested and observed for skin tumors and other lesions for 52 weeks. Neither Panoxyl nor gel influenced UV tumorigenesis or carcinogenesis under these experimental conditions. In hr/hr mice there was this time no enhancement of DMBA-induced tumorigenesis by the gel, and a slight reduction of carcinogenesis. In addition, several groups of SENCAR mice (which have been bred for high sensitivity to skin carcinogenesis) were also treated, with acetone alone, with a single application of DMBA alone, with Panoxyl alone, or with DMBA followed by treatment with the ointment gel or with Panoxyl twice a week throughout the experiment. In SENCAR mice there was no difference between the results of treatment with DMBA followed by Panoxyl, or DMBA followed by gel, and both substances tended to reduce the tumorigenicity of DMBA alone, and Panoxyl or gel showed no tumorigenicity of their own. The total dose of UV used in this study was lower than that used in the first study. This reduction in dose significantly increased the tumorigenic effect of UV.
Carcinogenesis 1988 May
PMID:Skin tumorigenesis and carcinogenesis studies with 7,12-dimethylbenz[a]anthracene, ultraviolet light, benzoyl peroxide (Panoxyl gel 5%) and ointment gel. 313 Feb 5

HRA/Skh hairless mice were investigated for their sensitivity to initiation and promotion by chemicals because of (a) the known sensitivity of these mice to photocarcinogenesis, (b) their low background papilloma incidence (2/3000 mice under 1 year of age) and (c) ease of treatment and identification of tumors, in the absence of hair. Employing a variety of treatments with 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter, it was found that the strain was susceptible to both initiation and promotion. Papilloma incidence was at least equivalent to that observed with other sensitive mouse strains. Following initiation with 2.56 micrograms DMBA, papilloma development was promoter-concentration-dependent, resulting in 22.5 papillomas/mouse at 20 weeks in animals administered 5 micrograms TPA. In the absence of DMBA initiation, TPA treatment was weakly carcinogenic in HRA/Skh mice. This treatment induced a dose-dependent increase in papillomas, one of which progressed to a keratoacanthoma-like tumor after 65 weeks. These results show that HRA/Skh mice are highly sensitive, not only to UV carcinogenesis, but also to chemical initiation and promotion of skin papillomas.
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PMID:Sensitivity of HRA/Skh hairless mice to initiation/promotion of skin tumors by chemical treatment. 313 22

An animal experiment is presented in which three groups of albino hairless mice (Skh-hr 1) were exposed to daily doses of either UV-B or UV-A to study carcinogenesis. The UV-A was filtered carefully so as to eliminate contaminating UV-B. The doses required for acute effects (erythema and edema) were also determined for the two radiation modalities. In order to study the relative carcinogenic risks of exposures to UV-A and to UV-B, for both modalities, the doses causing skin tumors were compared to the doses required for eliciting acute effects in the skin. In the experiment on carcinogenesis all animals developed tumors, the ones exposed to UV-A as well as the ones exposed to UV-B. A striking difference, however, was that the induction times of the first tumors showed a larger spread in the mice exposed to UV-A than in the UV-B groups. Also, the development of successive tumors in each individual mouse was more spread in time in the UV-A group. A second difference between the effects on the skin was that in the animals exposed to UV-B no skin reactions were seen until the tumors developed. However, in most UV-A exposed animals, a marked scratching, probably caused by severe itching, and hyperkeratosis preceded the development of the tumors. Histologically at least 60% of the larger tumors induced by UV-A appeared to be squamous cell carcinomas. This finding is very similar for UV-B induced tumors. The elastic fibers in the UV-A exposed animals were also examined and actinic elastosis was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The carcinogenic risks of modern tanning equipment: is UV-A safer than UV-B? 317 87

There is considerable evidence that retinoids, including retinoic acid, prevent or normalize many malignant transformations. Contrary reports are few in number and are often problematic in design or interpretation. The mechanism of action of retinoids in differentiation and in neoplasia is not understood. The effects, however, are multifarious, and may be exerted directly on normal tumor cells, or indirectly via cytotoxic mechanisms and the immune system. After extensive testing and after almost 25 years of use on human skin, retinoic acid has not been found to be a carcinogen. When applied topically to non-irradiated mouse skin for up to 18 months it does not produce tumors (130). It was also negative in the Ames test. Moreover, the role of retinoic acid in normal differentiation of skin and mucous membranes appears to make it a physiologic necessity. Since UV radiation apparently destroys epidermal vitamin A (127, 128), its metabolite, retinoic acid, may need to be replenished continuously. The extreme vulnerability of the hairless mouse to UV radiation makes it a valuable animal for many photobiologic studies, including studies of carcinogenesis. However, this same extraordinary vulnerability means that we must be cautious in making casual extrapolations to humans. This problem is compounded when active topical agents are added, especially when application is made to the entire dorsum of the mouse, in contrast to limited areas of human skin. In most cases, animal studies have to be interpreted very carefully. The final judgment must rest on the human experience.
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PMID:Retinoic acid and photocarcinogenesis--a controversy. 330 3


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