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Query: UMLS:C0920652 (skin irritant)
 188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The DNA content and the changes in cellular and nuclear size of isolated regenerating mouse epidermal basal cells were studied after topical application of the skin irritant cantharidin and the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to the back skin of hairless mice. The DNA and protein contents of isolated basal cells were stained with propidium iodide and fluorescein isothiocyanate, respectively, and analysed by flow cytometry using the total protein fluorescence as an estimate of cell size and the DNA fluorescence pulse width as an estimate of nuclear size. Transmission electron microscopy was used to identify cells sorted from regions in the bivariate DNA/protein distributions. The results showed that both chemicals induced an increase in cellular as well as nuclear size of the basal cells. The increase in size was higher in TPA treated than in cantharidin treated animals, and the bivariate DNA/protein distributions of TPA treated cells differed from those of cantharidin treated cells in that two subpopulations of cycling keratinocytes could be identified. These deviations are probably related to the higher proliferative response observed after TPA treatment and the possibility that proliferative subpopulations in epidermis respond differently to TPA. It may reflect mechanisms providing for a growth advantage of initiated cells, important in tumor promotion. About 8% of the cells in the suspensions from treated animals were non-cycling non-keratinocytes, probably infiltrating leukocytes. The results indicate a strong correlation between rapid regenerative cell cycle progression, i.e., reduced G1 transit time and increased cellular and nuclear size.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multivariate flow cytometry of epidermal regeneration provoked by a skin irritant and a tumor promoter. 157 92

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.
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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

Dodecylbenzene in various concentrations, dissolved in acetone to a final volume of 50 microliters, was applied twice a week for 78 weeks to the back skin of hairless mice, with or without pretreatment with 51.2 micrograms 9,10-dimethyl-1,2-benzanthracene (DMBA). A negative control group was painted with acetone only and a positive control group was given a single application of 51.2 micrograms DMBA. A few tumours developed but there was no significant skin tumorigenicity--that is, occurrence of benign or malignant tumours--by acetone alone, or by 16% dodecylbenzene. More tumours developed in the group treated with 80% dodecylbenzene than in the group treated with acetone alone or with 16% dodecylbenzene, but there was no significant difference between treatments with 16% and 80% dodecylbenzene. There was only a suggestive increase in tumorigenesis in the group given 51.2 micrograms DMBA and thereafter painted with 40% dodecylbenzene twice a week compared with the group given 51.2 micrograms DMBA once. As regards histologically malignant tumours--that is, carcinogenicity--the group treated twice a week with 16% dodecylbenzene alone developed two skin malignancies, whereas only one carcinoma was observed in the group treated with 80% dodecylbenzene; both results are non-significant. There was only a suggestive increase in the occurrence of skin malignancies in the group treated with DMBA followed by 40% dodecylbenzene compared with that treated with DMBA alone. As regards other tumours, treatment with 80% dodecylbenzene led to six lymphomas in 56 animals, whereas the acetone control group had two lymphomas in 56 animals, a difference which is only suggestive. DMBA alone and DMBA followed by dodecylbenzene gave five and four lymphomas, respectively. There was no significant difference between controls and dodecylbenzene painted animals for lung adenomas or other tumours. A pronounced epidermal hyperplasia, an increase in melanin pigment ("blue spots"), pigment leakage, and skin ulcerations were seen, mainly after 80% dodecylbenzene and after DMBA followed by 40% dodecylbenzene. There was no obvious increase in amyloidosis after continual treatment with 80% dodecylbenzen. The results indicate that 80% dodecylbenzene alone is weakly tumorigenic but not carcinogenic in the skin of hairless mice, and it tends slightly to enhance DMBA initiated tumorigenesis and carcinogenesis. Dodecylbenzene may be a weak inducer of malignant lymphomas. It is a fairly strong skin irritant and may increase amyloidosis.
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PMID:Studies of the carcinogenesis and tumorigenesis of skin applications of dodecylbenzene on hairless mice. 235 57

The cell cycle traverse of epidermal basal cells 24 h after in vivo exposure of ultraviolet B (UVB) irradiation was studied by immunochemical staining of incorporated bromodeoxyuridine (BrdU) and bivariate BrdU/DNA flow cytometric analysis. The results were compared with the cell kinetic patterns following topical application of the skin carcinogen methylnitrosourea (MNU) as well as the skin irritant cantharidin. Hairless mice were injected intraperitoneally with BrdU 24 h after treatment of their back skin with either a minimal erythema dose of UVB, or a single application of MNU or cantharidin dissolved in acetone. The cell cycle traverse of the BrdU-labelled cohorts of epidermal basal cells were then followed for the subsequent 12 h. At 6 h after BrdU-injection, when all labelled cells in the control group as well as in the cantharidin group had left the S phase, the bivariate distributions of the UVB-exposed and the MNU group showed that BrdU-positive cells were still present in S phase. Hence, UVB irradiation, similar to the carcinogen MNU, prolonged the S phase duration in some of the basal cells. At 12 h after pulse labelling, however, BrdU-positive cells from UVB-exposed mice were re-entering S phase from G1 phase, indicating that UVB irradiation induced a shortening of the cell cycle time as well, similar to the response observed after cantharidin. The present data can not tell whether these cells also were delayed in S phase. Thus, the cell cycle traverse in hairless mouse epidermis 24 h after in vivo exposure to UVB seemed to be a combination of the cell kinetic effects following chemical skin carcinogens and skin irritants. UVB irradiation induced both a delay in transit time through S phase, probably due to DNA damage and subsequent repair, as well as a reduction in the total cell cycle time consistent with rapid regenerative proliferation.
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PMID:The epidermal cell kinetic response to ultraviolet B irradiation combines regenerative proliferation and carcinogen associated cell cycle delay. 278 Aug 31