TY - JOUR
T1 - The effects of dexamethasone on mouse skin initiation and aryl hydrocarbon hydroxylase
AU - Thompson, Sara
AU - Slaga, Thomas J.
N1 - Funding Information:
IT HAS been shown by Belman and Troll \[1\] that a series of steroidal anti-inflammatory agents inhibited, in a dose dependent manner, tumor promotion by croton oil in mouse skin (dexamethasone > Schering No. 11572 > pred-nesolone > hydrocortisone > cortisone) which correlated with their anti-inflammatory activities in mouse skin. They also showed that dexamethasone inhibited croton oil induced hyperplasia. Nakai \[2\] also showed that MC-induced sarcomas in mice was inhibited by steroids in the order dexamethasone > triamcinolone > methyl prednesolone > hydrocortisone > cortisone and that this correlated with their anti-inflaramatory potencies. We later showed that dexamethasone could completely Accepted 22 October 1975. *This work was supported in part by grant CA-13155 from the National\[C ancer Institute of NIH.
PY - 1976/5
Y1 - 1976/5
N2 - Mouse epidermis contains a NADPH dependent aryl hydrocarbon hydroxylase (AHH), which is inducible by polycyclic hydrocarbons. The effects of dexamethasone, an anti-inflammatory steroid, on skin carcinogenesis and on mouse epidermal AHH were investigated. Dexamethasone was found to reduce tumor initiation by both 3-methylcholanthrene and 7,12-dimethylbenz(a)anthracene. Dexamethasone applied topically to mice at a dose level of 25 or 75 μg slightly stimulated the AHH activity in mouse epidermis with peaks of 150 or 180% of controls, respectively, at 2 hr and a return to control level by 4 hr. This was followed by a weak inhibition between 4 and 8 hr after treatment with either dose of dexamethasone. Dexamethasone did not inhibit benz(a)-anthracene-induced AHH activity in vitro when added to the assay, even at concentrations greater than equimolar amounts to benzo(a)pyrene. However, if dexamethasone or fluocinolone acetonide were applied topically with 3-methycholanthrene (MC), they inhibited the MC induction of AHH by at least 50% between 4 and 18 hr after simultaneous treatment. The more potent anti-inflammatory steroids, fluocinolone acetonide and fluclorolone acetonide, had a greater inhibitory effect on MC induction of AHH after simultaneous treatment. The mouse skin tumor promoters, croton oil and 12-0-tetradecanoylphorbol-13-acetate, had only a weak stimulatory effect on the AHH activity. The mechanism by which the anti-inflammatory steroids inhibit tumor initiation may be related to their ability to inhibit the metabolism of polycyclic hydrocarbons to their ultimate carcinogenic form(s).
AB - Mouse epidermis contains a NADPH dependent aryl hydrocarbon hydroxylase (AHH), which is inducible by polycyclic hydrocarbons. The effects of dexamethasone, an anti-inflammatory steroid, on skin carcinogenesis and on mouse epidermal AHH were investigated. Dexamethasone was found to reduce tumor initiation by both 3-methylcholanthrene and 7,12-dimethylbenz(a)anthracene. Dexamethasone applied topically to mice at a dose level of 25 or 75 μg slightly stimulated the AHH activity in mouse epidermis with peaks of 150 or 180% of controls, respectively, at 2 hr and a return to control level by 4 hr. This was followed by a weak inhibition between 4 and 8 hr after treatment with either dose of dexamethasone. Dexamethasone did not inhibit benz(a)-anthracene-induced AHH activity in vitro when added to the assay, even at concentrations greater than equimolar amounts to benzo(a)pyrene. However, if dexamethasone or fluocinolone acetonide were applied topically with 3-methycholanthrene (MC), they inhibited the MC induction of AHH by at least 50% between 4 and 18 hr after simultaneous treatment. The more potent anti-inflammatory steroids, fluocinolone acetonide and fluclorolone acetonide, had a greater inhibitory effect on MC induction of AHH after simultaneous treatment. The mouse skin tumor promoters, croton oil and 12-0-tetradecanoylphorbol-13-acetate, had only a weak stimulatory effect on the AHH activity. The mechanism by which the anti-inflammatory steroids inhibit tumor initiation may be related to their ability to inhibit the metabolism of polycyclic hydrocarbons to their ultimate carcinogenic form(s).
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U2 - 10.1016/0014-2964(76)90174-2
DO - 10.1016/0014-2964(76)90174-2
M3 - Article
C2 - 821758
AN - SCOPUS:0017074756
SN - 0014-2964
VL - 12
SP - 363
EP - 370
JO - European journal of cancer
JF - European journal of cancer
IS - 5
ER -