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

Our recent studies have shown that polyphenols present in green tea (GTP) possess significant antigenotoxic activity and afford protection against polycyclic aromatic hydrocarbon-induced skin tumor initiation in mice. In this study we assessed the effect of oral feeding and topical application of GTP on ultraviolet B (UVB) radiation-induced skin carcinogenesis in female SKH-1 hairless mice. Chronic oral feeding of GTP (0.1%, w/v) in drinking water resulted in significantly (P less than 0.01) lower tumor yield (percent of animals with tumors and number of tumors per mouse) and extended TDT50 (P less than 0.05), as compared to animals receiving normal drinking water. Topical application of GTP before UVB irradiation also afforded protection against photocarcinogenesis; however, the protective response was lower than that observed by oral feeding of GTP in drinking water. These results, in conjunction with our prior publications, suggest that consumption of green tea may reduce the risk of some forms of human cancer induced by both physical and chemical environmental carcinogens.
Carcinogenesis 1991 Aug
PMID:Protection against ultraviolet B radiation-induced photocarcinogenesis in hairless mice by green tea polyphenols. 186 Jan 73

Groups of hairless mice were painted with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) dissolved in reagent-grade acetone in various doses, dose fractions and concentrations. The animals were examined once a week for an appropriate time period and skin tumors were registered and classified as tumors (all tumors appearing) and as malignant tumors. The results show that dividing a particular dose of DMBA into an increasing number of applications was the factor that had the greatest tumorigenic and carcinogenic effect. This was found for total doses of 100, approximately 50 and approximately 26 micrograms DMBA. Similarly, increasing the size of the dose increased the effect on the tumor and carcinoma crop, but to a less pronounced event than splitting the dose into several fractions. The most striking of these effects was that a single dose of 51.2 micrograms DMBA gave a tumor rate of approximately 40%, whereas the same dose divided into 50 doses of 1 microgram gave a tumor rate of almost 100%. The final tumor yield increased from approximately 45 tumours per 32 animals after a single dose of 51.2 micrograms DMBA to approximately 250 tumors per 32 animals after 50 applications of 1 microgram DMBA. The final number of carcinomas per 32 animals was one carcinoma after a single application of 51.2 micrograms DMBA, and 40 carcinomas after 50 applications of 1 microgram DMBA. The paper includes a discussion on how these findings may be explained in terms of the complicated series of events that constitutes carcinogenesis. If it is biologically plausible to regard agents for which there is sufficient evidence for carcinogenicity in experimental animals as representing a carcinogenic risk to humans, then it may also be plausible and prudent to infer that the dose schedule that represents the highest tumorigenic hazard for mouse skin may generally also be the dose schedule that involves the highest risk for humans. Thus, repeated exposure to small doses may be the most hazardous situation. This is unfortunately the way many human beings are exposed to cigarette smoke, sunshine and carcinogens in food, water, air and at the work place. As shown in a previous paper, an increasing time interval between each dose may also increase the risk.
Carcinogenesis 1991 Mar
PMID:The skin tumorigenic and carcinogenic effects of different doses, numbers of dose fractions and concentrations of 7,12-dimethylbenz[a]anthracene in acetone applied on hairless mouse epidermis. Possible implications for human carcinogenesis. 190 Dec 52

Detection of micronuclei (MN) in skin cells from HRA/Skh hairless mice treated with chemical or physical agents may prove informative in qualitative and quantitative studies of skin carcinogenesis. MN induction and cell survival were estimated in cytokinesis-blocked keratinocytes, cultured for 4 days in vitro, after a single topical dose of various organic compounds. Treatment with 2.56 micrograms (10 nmol) 7,12-dimethylbenz[a] anthracene (DMBA) resulted in maximal MN induction in cells removed from skin 12-24 hr after topical administration (79-88 MN/1,000 cells compared with 10-16 MN/1,000 cells in acetone-treated controls). Even in cells removed only 1 hr after DMBA treatment, a significant increase in MN was evident. However, to allow sufficient time for metabolic activation, a sampling time for of 24 hr was adopted for all test substances. Dose-dependent increases in MN were observed with DMBA, benzo[a]pyrene, chrysene, and urethane. Increased numbers of micronucleated cells were detected at the lowest doses administered in the present study (0.128, 0.5, 50, and 50 micrograms, respectively). Although reduced cell recovery occurred following exposure of mice to acetone, pyrene, and other chemicals, there was no evidence that cytotoxicity contributed to MN scored in keratinocytes. Moreover, the probable noncarcinogen, pyrene, failed to induce MN at doses from 2.5 micrograms to 2.5 mg/mouse. These results show that it is possible to assess chemical exposure in skin by measuring cell survival and skin genotoxicity by measuring MN induction in cultured keratinocytes. The available data suggest that MN induction may be a useful indicator of the carcinogenic potential of chemicals applied to the skin.
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PMID:Micronuclei in mouse skin cells following in vivo exposure to benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, chrysene, pyrene and urethane. 190 14

Groups of hairless mice were painted with urethan alone, with the complete carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) alone, and with an initiating dose of DMBA followed by continual treatment with urethan or with the promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). The animals were examined once a week for an appropriate time period. Malignant and non-malignant skin tumors were registered and classified. Lung adenomas and other internal tumors were also counted. The results show that all types of treatment produced skin tumors, some of which were malignant. When urethan was used lung adenomas also appeared, along with a few other tumors. The results show that a 10% solution of urethan in acetone is a significant promoter, showing synergistic increase of DMBA-induced skin tumors, but urethan is not as strong a promoter as 10 nmol TPA. Urethan is said to be the pure initiator of skin carcinogenesis. Previously the author has shown that urethan alone is a complete carcinogen and here it is shown that it is also a promoter. Hence, the current hypothesis of urethan as a pure initiator in skin carcinogenesis has been disproved.
Carcinogenesis 1991 May
PMID:Urethan (ethyl carbamate) is an effective promoter of 7,12-dimethylbenz[a]anthracene-induced carcinogenesis in mouse skin two-stage experiments. 190 92

Citral inhibits the formation of retinoic acid from retinol in mouse epidermis. Since skin-carcinogenesis is sensitive to retinoid status, and retinoic acid may be the active form of vitamin A in the epidermis, citral was tested for its ability to modulate tumor promotion in a two-stage skin-carcinogenesis study in hairless mice. The dorsal skins of female skh/hr1 mice were initiated with 0.1 mumol dimethylbenzanthracene, and tumors were promoted by twice-weekly application of 10 nmol of tetradecanoylphorbol-13-acetate (TPA) for 20 weeks. Prior to each TPA application groups were dosed with 0, 1 mumol, or 10 mumol citral. Citral had a dose-dependent inhibitory effect on tumor-production in the TPA promoted groups. At 10 weeks of promotion the percentage of mice with tumors were 88%, 72% and 60%, for the 0, 1 and 10 mumol citral treated groups, and the numbers (mean +/- S.D.) of tumors per affected animal were 7.3 +/- 6.6, 3.9 +/- 4.2, and 3.7 +/- 3.5, respectively. At 15 weeks of promotion the tumor incidence was 96%, 96% and 84%, respectively, and the number of tumors per affected animal were 9.5 +/- 6.8, 7.2 +/- 4.6 and 4.5 +/- 3.3, respectively. Again the affected mice in the high dose citral group had significantly fewer tumors. When the study was terminated at 20 weeks of promotion all mice had at least one tumor, but the number of tumors per affected mouse were lower in the citral treated groups. These findings concur with the proposal that there is a retinoid requirement for skin tumor promotion, and establishes that anti-retinoids have potential uses as modulators of carcinogenesis.
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PMID:Modulation of tumor promotion in mouse skin by the food additive citral (3,7-dimethyl-2,6-octadienal). 200 50

The proliferative responses induced in hairless mouse epidermis after application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the skin irritant cantharidin were investigated. Doses known to give the same degree of hyperplasia were chosen. Mice were pulse-labeled with bromodeoxyuridine (BrdUrd) 30 min prior to or 24 h after a single application of either cantharidin or TPA, and thereafter killed at various time intervals. The basal cells were isolated from epidermis, fixed in 70% ethanol and prepared for bivariate BrdUrd/DNA flow cytometric analysis. Cells pulse-labeled in S phase 30 min prior to treatment with cantharidin or TPA were slightly delayed in their progression through S phase and temporarily blocked in G2 phase. However, they were still able to re-enter S phase 18 h later, indicating a shortening of the G1 phase. Cells pulse-labeled 24 h after treatment had a considerably reduced cell cycle time, i.e. reduced G1 transit time. Hence, the wave of cells entering S phase from 16 h after injury could be explained by an immediate reduction in G1 transit time, without assuming recruitment of temporarily resting G0/G1 cells. Although cantharidin caused the longest initial delay in cell cycle progression, the subsequent proliferative response was less pronounced than that provoked by TPA. Rapid proliferation may allow for clonal expansion of initiated cells. The higher ability of TPA to induce rapid proliferation, apparently without causing any severe initial cell damage, may thus be related to its higher tumor promoting ability.
Carcinogenesis 1991 May
PMID:A comparison between the epidermal regenerative responses provoked by a skin irritant and a tumor promoter using anti-BrdUrd/DNA flow cytometry. 202 47

A monoclonal antibody specific for cyclobutane thymine dimers in DNA was used in immunofluorescence studies to detect these lesions in skin sections taken from hairless mice that had been irradiated with UV-B. The dimer-specific fluorescence in epidermal cell nuclei was quantified with fluorescence microscopy through computer-mediated image processing and analysis. After a UV-dose of 500 J/m2, thymine dimers could easily be detected. Rapid removal of these lesions in vivo was observed during the first 4 h after exposure, but at 24 h approximately 40% of the dimers still persisted. Thymine dimers accumulated in the skin of mice subjected chronically to a dose regimen of 1000 J/m2 UV-B per day. In the first week strong accumulation of dimers was observed. At day 3 to 4 it reached a maximum, after which a decrease to a more constant level occurred. Concomitant with this decrease the number of epidermal cell layers increased after the first week. After 3 months of irradiation, mice started to develop skin tumors. At that time point the epidermis had thickened to contain up to 10 cell layers, compared to 1-2 layers in unirradiated mice, but thymine dimers were still induced.
Carcinogenesis 1991 May
PMID:Induction, repair and accumulation of thymine dimers in the skin of UV-B-irradiated hairless mice. 202 50

An increase in skin cancer incidence due to an increase of solar ultraviolet (UV) radiation is one of the best quantitated effects of stratospheric ozone depletion. Until now, estimates of effective UV dosages could not be based on spectral data on carcinogenicity. Instead the spectral dependence of sunburn or mutations was used. These data contained little information on longwave ultraviolet radiation (UVA: 315-380 nm). Recently, in hairless mice, experimental data have become available on the carcinogenic effectiveness of the ultraviolet, including UVA. From these new data we can estimate the effect of ozone depletion on the ambient annual carcinogenic UV dose. We find that a 1% decrease in ozone yields a 1.56% increase in annual carcinogenic UV; this value is not strongly dependent on geographical latitude. From this result, combined with the dose-response relationship for UV carcinogenesis, we conclude that for a 1% decrease in total column atmospheric ozone an increase of 2.7% in non-melanoma skin cancer is to be expected.
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PMID:Ozone depletion and increase in annual carcinogenic ultraviolet dose. 208 31

In order to evaluate the role of beta-carotene as an inhibitor of skin carcinogenesis, hairless female HRA/Skh mice were treated with the initiator 7,12-dimethylbenz[a]anthracene (DMBA) and with the promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), and were fed a balanced diet free from vitamin A either with or without gavage-administered beta-carotene. There was no evidence of avitaminosis A or differences in body weight in mice deprived of beta-carotene and vitamin A, compared with those given 290 or 1430 IU beta-carotene/kg per day. Mice fed with normal animal feed pellets displayed a significantly higher body weight (28.5 +/- 1.95 g) compared with mice on the special diet (25.7 +/- 1.9 g), and also displayed a higher papilloma yield. However animals on the special diet, fed with beta-carotene from weaning, displayed significantly lower numbers of papillomas per mouse. This lower papilloma yield was evident particularly between 12-24 weeks after commencement of the study, which coincided with the period of maximum tumor yield in DMBA/TPA-treated mice. The characteristic regression of papillomas after that time points to the reversibility of many earlier papillomas, and their dependence on continued TPA administration. Evaluation of carcinomas in mice on the various dietary regimes showed there was no significant difference between any group, including those fed with beta-carotene continuously from weaning. The present results demonstrate that a sustained dietary intake of beta-carotene from 3 weeks of age partially suppressed the growth of papillomas, but did not affect the course of malignant progression in DMBA/TPA-treated HRA/Skh mice. It is evident that beta-carotene predominantly affects TPA-dependent papillomas, which possess reversible properties and have a low probability of progression to form carcinomas.
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PMID:Effects of beta-carotene on chemically-induced skin tumors in HRA/Skh hairless mice. 211 29

Ultrastructural morphometric characteristics of basal keratinocytes in hairless mouse epidermis were analyzed statistically. The following variables were assessed: (i) low versus physiological osmolality during fixation, (ii) alterations induced by a 2-stage carcinogenesis regimen using DMBA and TPA, (iii) criteria for a cell being dark versus being clear, (iv) inter-observer variation. The results show that with low fixation osmolality most basal cells swell and become electron lucent. The few cells which apparently do not swell stand out as shrunken electron dense dark cells. Morphometrically they are more differentiated than clear cells, but do share many features with the basal cell type which appears after fixation in a buffer of physiological osmolality. Iso-osmolality during fixation seems to induce a homogeneous basal cell population of relatively electron dense cells without typical dark and clear elements. Treatment with DMBA/TPA induces not only intercellular edema and reduced desmosomal contacts, but causes injury to the plasma membrane leading to hydropic changes in the cells. This general intra- and intercellular DMBA/TPA induced hydration might induce secondary compression of some of the cells, leading to an increased number of compressed dark cells. It is, however, only after fixation in low buffer osmolality that these effects of DMBA/TPA are statistically significant and clearly observable. The inter-person variation was, apart from a few instances, either not statistically significant or did not interfere with the other effects. We did not find clear arguments in favor of the view that dark cells are primitive epidermal stem cells. They seem only to reflect non-specific toxic effects of tumor promoters, which appear only under certain fixation conditions, that have been used by most authors. The results suggest that dark and clear cells are mainly a consequence of the degree of cellular hydration.
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PMID:Morphometric evaluation of dark and clear epidermal basal cells during early 2-stage chemical skin carcinogenesis in the hairless mouse using two different fixation methods. 211 28


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