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

Epidemiological studies suggest that the incidence of cancer increases with age in both human and animal populations and that declining physiologic condition associated with aging might be responsible. Experimentally, the reverse has been most often observed, that is, older animals appear less susceptible to the induction of UV-carcinogenesis. Thus, we examined several biochemical parameters of epidermal macromolecular synthesis in hairless mice in an effort to gain insight into the role these processes play in physiological aging and their relationship to carcinogenesis. SKh-Hr-1 hairless mice were randomized into two groups (UV-irradiated and non-irradiated controls) and were two months of age at the start of irradiation and biochemical analyses. The UV group received 0.028 sunburn units (SBUs) daily (5 days wk-1) for 16 months from 40 watt BZS-WLG lamps. Stratum corneum turnover rates (SCR), cell label index (CLI), protein, DNA and RNA synthesis, and ornithine decarboxylase (ODC) induction were determined at monthly intervals over a period of two years. There were no age-related tendencies observed in SCR. CLI increased with age. Chronic, low-dose UV had no effect upon either of these parameters. Epidermal capacity for DNA and protein synthesis increased with age from 2 months to 12-15 months at which time both parameters peaked and then began to decline. UV significantly reduced (P < 0.04) the magnitude of DNA synthetic capacity at peak periods of synthesis but had no effect upon protein synthesis. RNA synthetic rates declined with age, reaching their lowest levels at 24 months. Further, a significant reduction (P < 0.001) in ODC inducibility occurred with advancing age.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical parameters of epidermal aging in the hairless mouse and the relationship to UV-carcinogenesis. 751 73

Cyclobutane pyrimidine dimers (CPD) are the predominant DNA lesions induced by UV-B radiation, among these lesions thymine dimers are most frequent. Although UV-A radiation may also induce CPD, it has been found that equally cytotoxic or equally mutagenic UV-A and UV-B doses do not induce equal amounts of CPD, indicating that other DNA adducts contribute to the UV-A effects. Thus far it has not been established whether this finding can be extrapolated and also holds true for the more complex biological endpoint of skin cancer. Therefore, we compared thymine dimer levels during skin cancer induction by combined UV-A and UV-B daily exposures with the levels from equally carcinogenic daily UV-B exposures. From control experiments it was known that both groups would react similarly regarding the occurrences of carcinomas, with a median latency time of 170 +/- 10 days. After 50, 106 and 151 days of irradiation eight hairless mice (SKH:HR1) from both groups were euthanized and thymine dimers in epidermal cell suspensions were quantified by flow cytometry. Staining on DNA content enabled us to quantify thymine dimers in G0/G1-phase, in S-phase and in G2M-phase subpopulations. Both in total epidermal cell populations and in subpopulations of replicating epidermal cells thymine dimer levels were significantly lower in the UV-A/B combination group than in the UV-B group (0.010 < P < 0.025 and P < 0.005 respectively). This indicates that the carcinogenicity of UV-A relative to that of UV-B is not properly measured by thymine dimers and that other DNA lesions than CPD, for example, from reactive oxygen species, are likely to contribute to UV-A carcinogenicity.
Carcinogenesis 1995 Oct
PMID:Substitution of equally carcinogenic UV-A for UV-B irradiations lowers epidermal thymine dimer levels during skin cancer induction in hairless mice. 758 51

Solar radiations (UV A and B) can cause epidermis photoaging and skin cancers. These frequently irreversible effects result from the in situ generation of free radicals. However, it has been noted that nutritional factors can modulate photochemical damage, in particular the common carotenoids present in food, which can be considered as potential prophylactic agents against carcinogenesis. We investigated the effect of UV A and B radiations on the skin of the SKH1 hairless mouse fed a diet either lacking in vitamin A or supplemented with retinol, beta-carotene or astaxanthin. The latter is an oxygenated carotenoid (like canthaxanthin) without provitamin A activity and with strong singlet oxygen quenching ability. After analysing of vitamin status of each group (plasma retinol concentrations and hepatic reserves), we searched for UV-induced modifications of polyamine metabolism by measuring epidermal ornithine decarboxylase (ODC) activity and free polyamines concentration (putrescine, spermidine and spermine). In the basal state without irradiation, differences in ODC activity between groups were nonsignificant; but after UV stimulation, ODC increased markedly in the skin of vitamin A-deficient animals, much more than in other groups. Curiously, the addition of astaxanthin or beta-carotene to the regimen containing retinol reduced the protective effect of retinol alone. Regarding polyamines after irradiation, putrescine was significantly increased in the skin of deficient animals, in parallel with ODC activity. However, astaxanthin had a stronger inhibitory effect on putrescine accumulation than retinol, and decreased spermidine and spermine concentrations: this suggests a specific action on transglutaminases.
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PMID:Vitamin A status and metabolism of cutaneous polyamines in the hairless mouse after UV irradiation: action of beta-carotene and astaxanthin. 759 36

Ultraviolet (UV) radiation is a very common carcinogen in our environment, but epidemiological data on the relationship between skin cancers and ambient solar UV radiation are very restricted. In hairless mice the process of UV carcinogenesis can be studied in depth. Experiments with this animal model have yielded quantitative data on how tumor development depends on dose, time and wavelength of the UV radiation. In combination with epidemiological data, these experimental results can be transposed to humans. Comparative studies on molecular, cellular and physiological changes in mouse and man can further our fundamental understanding of UV carcinogenesis in man. This is likely to improve risk assessments such as those related to stratospheric ozone depletion, and to yield well-targeted intervention schemes, e.g. prescribing a specific drug or diet, for high-risk individuals.
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PMID:UV-induced skin cancer in a hairless mouse model. 764 87

Ultraviolet (UV) irradiation produces two major photoproducts, cyclobutane pyrimidine dimers (CPD) and (6-4) photoproducts. T4 endonuclease V (T4N5), which specifically repairs CPD, is encapsulated in liposomes. A previous study has shown that UV-induced carcinogenesis in mice was suppressed by the application of T4N5 liposomes. To confirm the suppressive effect, we applied T4N5 liposomes with repeated UVB exposure to hairless mice. At the end of the experiment, mice treated with T4N5 liposomes had 3.5 +/- 1.3 tumors per mouse, and control mice had 6.3 +/- 2.8 tumors per mouse. In addition, the incidence of tumors was reduced in T4N5 liposome-treated mice compared with controls. The pathological diagnosis of the tumors was not significantly different between two groups. Immunohistochemical analysis of p53 protein in UV-induced tumors showed that nearly half of the tumors in both groups were positive. When the biopsied normal-looking skin taken during the experiment was stained with p53 antibody, there was no significant difference of the timing of p53 protein expression between the control mice and T4N5 liposome-treated mice. These results confirmed that CPD plays a pivotal role in UV carcinogenesis, although the molecular mechanisms of the suppression by T4N5 liposomes should be further clarified.
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PMID:Reduction of ultraviolet-induced skin cancer in mice by topical application of DNA excision repair enzymes. 765 67

We have investigated UV-B-induced skin tumors of hairless SKH-HRA mice for alterations in the p53 gene and for mutations in either of the three ras genes. Out of 32 tumors screened, only one contained a ras mutation, i.e. in codon 12 of the K-ras gene. Alterations in the p53 gene were much more abundant, as illustrated immunohistochemically by the accumulation of p53 protein in 75% of the tumor sections examined. Immunoreactivity was observed primarily in the proliferative cell compartment, but no clear correlation between p53 staining in tumor cells and histological parameters for malignancy was observed. Subsequent sequence analysis showed that point mutations in the p53 gene are detectable in 30% (nine out of 30) of the skin tumors examined. The majority of the mutations are located in codons 267 and 272, most likely originating from UV-B-induced photo-adducts at dipyrimidine sites in the non-transcribed strand. Codon 272 corresponds to the human codon 278, which is also a hotspot for p53 mutations in human non-melanoma skin cancers. Codon 267 matches the human codon 273, which does not contain a dipyrimidine site, but represents a CpG hotspot for p53 mutations in internal malignancies. Our results demonstrate that this hairless mouse model for UV-induced skin cancer corresponds closely to human non-melanoma skin cancers with respect to mutations in the p53 gene.
Carcinogenesis 1995 May
PMID:Frequent p53 alterations but low incidence of ras mutations in UV-B-induced skin tumors of hairless mice. 776 77

The effect of systemic treatment with the anti-inflammatory drug indomethacin on sun-induced skin carcinogenesis was examined in lightly pigmented hairless hr/hr C3H/Tif mice. Two groups of 20 mice were exposed to simulated solar ultraviolet radiation from one Phillips TL 12 and five Bellarium-S SA-1-12 tubes for 8 min/day, 4 days/week (daily dose was 12.6 kJ/m2, equivalent to 2.1 B-MED the basic minimal erythema dose). A mean dose of 1.8 mg kg-1 24 h-1 indomethacin was supplied to one of the two groups via the drinking water. The pharmacological treatment started on the first day of the trial and continued during the entire experiment. The time to first, second, and third tumour was significantly delayed in the group treated with indomethacin (P < 0.001). The mortality rate was higher in the indomethacin-treated group than in the group receiving no pharmacological treatment (P < 0.0005). Under the present conditions, our study suggests that indomethacin may be beneficial in protection against photocarcinogenesis.
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PMID:Effects of systemic indomethacin on photocarcinogenesis in hairless mice. 776 61

Excision repair of pyrimidine dimers was examined at the genome overall in three strains of hairless (hr/hr) and congenic wild-type mice, as well as in the expressed H-ras gene in hairless mice. The assay used a pyrimidine dimer-specific endonuclease from Micrococcus luteus and alkaline agarose gel electrophoresis. From 0 to 25% of endonuclease-sensitive sites were removed at the genome level in either hairy or hairless mice but about 50% were removed in the H-ras gene in hairless mice by 24 h after exposure to 5.4 J/cm2 UV (290-400 nm) irradiation. No differences were observed in the repair capacity between hairy and hairless mice, thus eliminating defective DNA repair as the explanation for the greater susceptibility to UV carcinogenesis in hairless mice.
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PMID:Pyrimidine dimer induction and removal in the epidermis of hairless mice: inefficient repair in the genome overall and rapid repair in the H-ras sequence. 801 16

Six-week-old male albino hairless mice (Hos: Hr-1) were exposed to a near-ultraviolet (UV) fluorescent sun lamp (33.5 kJ/m2/hr; wave length > 270 nm with a peak at 312.5 nm) to investigate the induction of oxidative DNA damage in epidermal cells. Significantly higher levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were detected in a dose-dependent manner in epidermis of mice exposed to near-UV than in those of control animals. The ratio of 8-OHdG in near-UV-exposed/unexposed control was 2.08 +/- 0.19 after 168 kJ/m2 exposure, P < 0.01; 3.49 +/- 0.36 after 335 kJ/m2 exposure, P < 0.01 (means +/- SE). The levels of 8-OHdG decreased with time after near-UV exposure, suggesting the presence of removal and/or repair mechanisms. This is the first report that oxidative DNA base modification is induced in vivo in epidermal cells by near-UV exposure. Oxidative DNA base modification may be one of the causes of sunlight-induced skin carcinogenesis.
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PMID:Formation of 8-hydroxy-2'-deoxyguanosine in epidermis of hairless mice exposed to near-UV. 802 54

Induction and removal of cyclobutane thymine dimers and (6-4)photoproducts were studied in epidermal DNA isolated from UV-exposed hairless mice. For the detection of DNA damage, lesion-specific monoclonal antibodies were used in an immunoslotblot assay. Following the exposure of mice to 3.0 kJ m-2 UV-B, substantial removal of both thymine dimers (66%) and (6-4)photoproducts (77%) was observed at 24 h after irradiation. No removal, however, was detected at 4 h after irradiation. In contrast, immunofluorescence data obtained previously showed a rapid initial dimer removal after irradiation with 1.0 kJ m-2 UV-B (A.A. Vink, R.J.W. Berg, F.R. De Gruijl, L. Roza and R.A. Baan, Carcinogenesis, 12 (1991) 861-864). Reinvestigation of the removal of dimers and (6-4)-photoproducts shortly after three different UV doses showed a rapid decreases of both lesions at 2 h after irradiation with 1.0 kJ m-2. The results obtained after irradiations with 2.0 and 3.0 kJ m-2 UV-B suggest a saturation of repair already at 2.0 kJ m-2. Cyclobutane dimers were found to be removed at a lower rate than (6-4)photoproducts.
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PMID:Removal of UV-induced DNA lesions in mouse epidermis soon after irradiation. 805 3


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