Inhibition by lipoxygenase inhibitors of 7-bromomethylbenz[a]anthracene-caused epidermal ornithine decarboxylase induction and skin tumor promotion in mice

Teruo Nakadate, Satoshi Yamamoto, Eriko Yokota, Ryuichi Kato

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

7-Bromomethylbenz[a]anthracene (BrMBA) has been shown to have a tumor-promoting action in mouse skin without an initial direct interaction with protein kinase C, which is believed to be a receptor for phorbol ester tumor promoters such as 12-0-tetradecanoylphorbol-13-acetate (TPA). An application of BrMBA to mouse dorsal skin caused epidermal ornithine decarboxylase (ODC) induction in a dose-dependent manner with a peak of activity at 12 h after the application. A single topical application of BrMBA failed to induce mouse ear edema formation, i.e. inflammation. However, repeated applications of BrMBA, i.e. twice a week for 3-4 times, caused a significant edema. Unlike TPA, BrMBA failed to stimulate the superoxide anion generation of rabbit peritoneal polymorphonuclear leukocytes. Lipoxygenase inhibitors such as 3,4,2',4'-tetrahydroxychalcone, nordihydroguaiaretic add, quercetin and 2,3,5-trimethyl-6-(12-hydroxy-5,10-dode-cadiynyl)-1,4-benzoquinone (AA861) effectively inhibited BrMBA-caused epidermal ODC induction and ear edema formation. In addition, BrMBA-caused skin tumor promotion was also potently inhibited by 3,4,2',4'-tetrahydroxy-chalcone and quercetin. These results indicate that a mechanism susceptible to lipoxygenase inhibitors plays a role not only in the TPA-caused but also in the BrMBA-caused epidermal ODC induction, skin inflammation and tumor promotion. It seems unlikely that superoxide anion generation is involved in the mechanism of BrMBA-caused skin tumor promotion.

Original languageEnglish
Pages (from-to)2053-2057
Number of pages5
JournalCarcinogenesis
Volume10
Issue number11
DOIs
Publication statusPublished - 1989 Nov

Fingerprint

Lipoxygenase Inhibitors
Ornithine Decarboxylase
Anthracene
Skin
Inhibitor
Mouse
Tumors
Tumor
Proof by induction
Tetradecanoylphorbol Acetate
Edema
Inflammation
Quercetin
Neoplasms
Superoxides
Ear
Negative ions
Chalcone
Protein Kinase C
Leukocytes

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Physiology
  • Behavioral Neuroscience
  • Cancer Research

Cite this

Inhibition by lipoxygenase inhibitors of 7-bromomethylbenz[a]anthracene-caused epidermal ornithine decarboxylase induction and skin tumor promotion in mice. / Nakadate, Teruo; Yamamoto, Satoshi; Yokota, Eriko; Kato, Ryuichi.

In: Carcinogenesis, Vol. 10, No. 11, 11.1989, p. 2053-2057.

Research output: Contribution to journalArticle

@article{d4828219ff9d4c15b41ba348e27378aa,
title = "Inhibition by lipoxygenase inhibitors of 7-bromomethylbenz[a]anthracene-caused epidermal ornithine decarboxylase induction and skin tumor promotion in mice",
abstract = "7-Bromomethylbenz[a]anthracene (BrMBA) has been shown to have a tumor-promoting action in mouse skin without an initial direct interaction with protein kinase C, which is believed to be a receptor for phorbol ester tumor promoters such as 12-0-tetradecanoylphorbol-13-acetate (TPA). An application of BrMBA to mouse dorsal skin caused epidermal ornithine decarboxylase (ODC) induction in a dose-dependent manner with a peak of activity at 12 h after the application. A single topical application of BrMBA failed to induce mouse ear edema formation, i.e. inflammation. However, repeated applications of BrMBA, i.e. twice a week for 3-4 times, caused a significant edema. Unlike TPA, BrMBA failed to stimulate the superoxide anion generation of rabbit peritoneal polymorphonuclear leukocytes. Lipoxygenase inhibitors such as 3,4,2',4'-tetrahydroxychalcone, nordihydroguaiaretic add, quercetin and 2,3,5-trimethyl-6-(12-hydroxy-5,10-dode-cadiynyl)-1,4-benzoquinone (AA861) effectively inhibited BrMBA-caused epidermal ODC induction and ear edema formation. In addition, BrMBA-caused skin tumor promotion was also potently inhibited by 3,4,2',4'-tetrahydroxy-chalcone and quercetin. These results indicate that a mechanism susceptible to lipoxygenase inhibitors plays a role not only in the TPA-caused but also in the BrMBA-caused epidermal ODC induction, skin inflammation and tumor promotion. It seems unlikely that superoxide anion generation is involved in the mechanism of BrMBA-caused skin tumor promotion.",
author = "Teruo Nakadate and Satoshi Yamamoto and Eriko Yokota and Ryuichi Kato",
year = "1989",
month = "11",
doi = "10.1093/carcin/10.11.2053",
language = "English",
volume = "10",
pages = "2053--2057",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "11",

}

TY - JOUR

T1 - Inhibition by lipoxygenase inhibitors of 7-bromomethylbenz[a]anthracene-caused epidermal ornithine decarboxylase induction and skin tumor promotion in mice

AU - Nakadate, Teruo

AU - Yamamoto, Satoshi

AU - Yokota, Eriko

AU - Kato, Ryuichi

PY - 1989/11

Y1 - 1989/11

N2 - 7-Bromomethylbenz[a]anthracene (BrMBA) has been shown to have a tumor-promoting action in mouse skin without an initial direct interaction with protein kinase C, which is believed to be a receptor for phorbol ester tumor promoters such as 12-0-tetradecanoylphorbol-13-acetate (TPA). An application of BrMBA to mouse dorsal skin caused epidermal ornithine decarboxylase (ODC) induction in a dose-dependent manner with a peak of activity at 12 h after the application. A single topical application of BrMBA failed to induce mouse ear edema formation, i.e. inflammation. However, repeated applications of BrMBA, i.e. twice a week for 3-4 times, caused a significant edema. Unlike TPA, BrMBA failed to stimulate the superoxide anion generation of rabbit peritoneal polymorphonuclear leukocytes. Lipoxygenase inhibitors such as 3,4,2',4'-tetrahydroxychalcone, nordihydroguaiaretic add, quercetin and 2,3,5-trimethyl-6-(12-hydroxy-5,10-dode-cadiynyl)-1,4-benzoquinone (AA861) effectively inhibited BrMBA-caused epidermal ODC induction and ear edema formation. In addition, BrMBA-caused skin tumor promotion was also potently inhibited by 3,4,2',4'-tetrahydroxy-chalcone and quercetin. These results indicate that a mechanism susceptible to lipoxygenase inhibitors plays a role not only in the TPA-caused but also in the BrMBA-caused epidermal ODC induction, skin inflammation and tumor promotion. It seems unlikely that superoxide anion generation is involved in the mechanism of BrMBA-caused skin tumor promotion.

AB - 7-Bromomethylbenz[a]anthracene (BrMBA) has been shown to have a tumor-promoting action in mouse skin without an initial direct interaction with protein kinase C, which is believed to be a receptor for phorbol ester tumor promoters such as 12-0-tetradecanoylphorbol-13-acetate (TPA). An application of BrMBA to mouse dorsal skin caused epidermal ornithine decarboxylase (ODC) induction in a dose-dependent manner with a peak of activity at 12 h after the application. A single topical application of BrMBA failed to induce mouse ear edema formation, i.e. inflammation. However, repeated applications of BrMBA, i.e. twice a week for 3-4 times, caused a significant edema. Unlike TPA, BrMBA failed to stimulate the superoxide anion generation of rabbit peritoneal polymorphonuclear leukocytes. Lipoxygenase inhibitors such as 3,4,2',4'-tetrahydroxychalcone, nordihydroguaiaretic add, quercetin and 2,3,5-trimethyl-6-(12-hydroxy-5,10-dode-cadiynyl)-1,4-benzoquinone (AA861) effectively inhibited BrMBA-caused epidermal ODC induction and ear edema formation. In addition, BrMBA-caused skin tumor promotion was also potently inhibited by 3,4,2',4'-tetrahydroxy-chalcone and quercetin. These results indicate that a mechanism susceptible to lipoxygenase inhibitors plays a role not only in the TPA-caused but also in the BrMBA-caused epidermal ODC induction, skin inflammation and tumor promotion. It seems unlikely that superoxide anion generation is involved in the mechanism of BrMBA-caused skin tumor promotion.

UR - http://www.scopus.com/inward/record.url?scp=0024417545&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024417545&partnerID=8YFLogxK

U2 - 10.1093/carcin/10.11.2053

DO - 10.1093/carcin/10.11.2053

M3 - Article

C2 - 2553289

AN - SCOPUS:0024417545

VL - 10

SP - 2053

EP - 2057

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 11

ER -