Volumetric Modifications of X‐Irradiated Keratinocytes

Klein‐Szanto, Andres J.; Rey, B.M. de; Cabrini, R. L.

doi:10.1111/j.1600-0560.1977.tb00884.x

Cited by 12 publications

(7 citation statements)

References 18 publications

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“…However, the use of thin (1-2 ,m) sections from plastic-embedded materials has made possible the observation of many morphological details previously not seen by light microscopy, including the dark basal keratinocytes (2,21). In addition, the observation of dark cells by light microscopy allows them to be easily quantitated.…”

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confidence: 99%

Studies on mechanism of action of anti-tumor-promoting agents: their specificity in two-stage promotion.

Slaga¹,

Klein‐Szanto²,

Fischer³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

111

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The effects of fluocinolone acetonide (FA), retinoic acid (RA), and tosylphenylalanine chloromethyl ketone (TPCK) on two-stage promotion after 7,12-dimethylbenzfaJ anthracene (DMBA) initiation in female Sencar mice were investigated. The two-stage promotion protocol was achieved by twice weekly applications of 2 sg of 12Otetradecanoylphorbol 13-acetate (TPA) for 2 weeks (stage I) followed by twice Carcinogenesis in the skin can be induced by the sequential application of a subthreshold dose of a carcinogen (initiation phase) followed by repetitive treatment with a noncarcinogenic tumor promoter. The initiation phase requires only a single application of either a direct-acting carcinogen or a procarcinogen (which has to be metabolized before being active) and is essentially irreversible; the promotion phase is initially reversible but later becomes irreversible. This system not only has provided an important model for studying carcinogenesis and for bioassaying carcinogenic agents, but it is also one of the best systems for investigating the effects of inhibitors of chemical carcinogenesis (1). Recent data from our laboratory suggest that the tumor promotion stage can be divided into two stages (2, 3). The first stage can be effectively brought about by limited applications of 12-0-tetradecanoylphorbol 13-acetate (TPA), or, to a lesser degree, of 4-0-methyl-TPA. Mezerein, a diterpene similar to TPA in its biochemical and morphological effects but a weak promoter, is a-potent stage II promoter when given repetitively after stage I promotion (2-4). The combined treatment after tumor initiation will give a tumor response similar to single-stage or complete promotion by TPA (3, 4).We have recently reported (3) that the only major biochemical and morphological difference between the effects of TPA and mezerein on the skin is the ability of TPA to induce a large number of dark basal keratinocytes, which suggests that these dark cells are important in stage I of promotion. The importance of these dark basal keratinocytes in tumor promotion was originally reported by Raick and coworkers (5-8). They found that TPA induced the appearance of these cells in the epidermis whereas ethylphenylpropiolate did not (5-8).The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 2251Inhibitors of tumor promotion have been useful in the identification of important events in tumor promotion. This has been especially true for anti-inflammatory steroids, retinoids, and protease inhibitors (1,(9)(10)(11)(12)(13)(14). These agents all are potent inhibitors of tumor promotion and chemical carcinogenesis in general (9-18). The purpose of this study was to determine the effects of some inhibitors of tumor promotion on the first and second stages of promotion and their effect on TPA-induced dark, basal keratinocytes. Tosylphenylalanyl chloromethyl ketone (TPCK) was found to inhibi...

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mentioning

confidence: 99%

Studies on mechanism of action of anti-tumor-promoting agents: their specificity in two-stage promotion.

Slaga¹,

Klein‐Szanto²,

Fischer³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

111

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“…Previous studies in our laboratory have shown the acanthogenic effect of radiation on the rat's tail epidermis Cabrini 1970, de Rey andKlein-Szanto 1972) . This acanthosis, studied as function of the elapsed postirradiation time using high doses of X-radiation, was mainly due to an increased volume of the basal keratinocytes and to a lesser extent to that of the spinous keratinocytes (Klein-Szanto, de Rey and Cabrini 1977) .…”

Section: Introductionmentioning

confidence: 87%

“…Four-day-old Wistar rats were locally irradiated as previously described (KleinSzanto andCabrini 1970, Klein-Szanto et al . 1977) .…”

Section: Methodsmentioning

confidence: 99%

“…The total delivered doses per group of five animals were 1000, 1250, 1500, 2000, 2500, 3000, 3500, 4000, 8000, 12 000 and 16 000 rad . All animals were sacrificed 4 days after irradiation ; in our previous experience with 16 000 rad this was the time at which the volume increment reached a maximum value (Klein-Szanto et al ., 1977) .…”

Section: Methodsmentioning

confidence: 99%

“…This acanthosis, studied as function of the elapsed postirradiation time using high doses of X-radiation, was mainly due to an increased volume of the basal keratinocytes and to a lesser extent to that of the spinous keratinocytes (Klein-Szanto, de Rey and Cabrini 1977) .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dose-dependent Volume Changes in X-irradiated Keratinocytes

Lanfranchi

Klein‐Szanto

Rey

et al. 1979

International Journal of Radiation Biology and Related Studies

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Comparison of differentiation patterns in 12-O-tetradecanoylphorbol-13-acetate-treated epidermis and fetal epidermis

1985

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12-O-Tetradecanoylphorbol-13-acetate (TPA)-treated adult epidermis as well as untreated fetal and adult epidermis were investigated to elucidate the effect of TPA in terms of cell differentiation using techniques of ultrastructural stereology. Twenty-four hours after a single application of TPA, the treated epidermis was characterized by involutional changes, i.e., increased volume density of intercellular spaces and of mitochondria, vacuoles, and cytoplasmic ground substance in the basal layer. However, 48 h after application, the TPA-treated epidermis was very similar to fetal epidermis, i.e., high volume density of nuclei ribosomes, rough endoplasmic reticulum, membrane-coating granules, and keratohyalin granules, and low volume density of bundled filaments in the upper layers. These stereological data indicate that the changes observed 48 h after TPA treatment were related not only to increased cell proliferation but also to inhibition of cell differentiation expressed as a reversion of the adult differentiation patterns and the acquisition of fetal characteristics in all epidermal layers.

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Volumetric Modifications of X‐Irradiated Keratinocytes

Cited by 12 publications

References 18 publications

Studies on mechanism of action of anti-tumor-promoting agents: their specificity in two-stage promotion.

Studies on mechanism of action of anti-tumor-promoting agents: their specificity in two-stage promotion.

Dose-dependent Volume Changes in X-irradiated Keratinocytes

Comparison of differentiation patterns in 12-O-tetradecanoylphorbol-13-acetate-treated epidermis and fetal epidermis

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