The effects of weak or non-carcinogenic polycyclic hydrocarbons on 7, 12-dimethylbenz[a]anthracene and benzo[a]pyrene skin tumor-initiation

Thomas J Slaga, L. Jecker, W. M. Bracken, C. E. Weeks

Research output: Contribution to journalArticle

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Abstract

Benzo[e]pyrene (B[e]P) inhibited 7,12-dimethylbenz[a]anthracene (DMBA) skin tumor-initiation in mice by 84%, whereas pyrene and fluoranthene inhibited DMBA initiation by 50 and 34%, respectively. However, B[e]P, pyrene and fluoranthene had either no significant effect or a slight enhancing effect on benzo[a]pyrene (B[a]P) skin tumor-initiation. In addition, B[e]P had essentially no effect on the initiating ability of (±)B[a]P-7β,8α-diol-9α,10α-epoxide. As a tumor-initiator, B[e]P was found to have very weak activity at a 252 μg/level (0.4 papillomas/mouse at 40 weeks) and no activity at 100 μg. When given at a dose of 100 μg twice weekly, B[e]P induced 2.1 papillomas/mouse at 30 weeks, and 25% of the mice had carcinomas at 40 weeks. However, B[e]P carcinogenic activity is weak when compared to B[a]P, which can induce a comparable tumor response at a dose of 5 μg twice weekly. When B[e]P was tested as a tumor promoter at a dose of 100 μg twice weekly after DMBA initiation, it induced 4.5 papillomas/mouse at 30 weeks and a 45% carcinoma incidence at 40 weeks, which was approximately twice as effective as B[e]P alone. The data show that B[e]P is a very weak tumor initiator, a weak complete carcinogen, a moderate tumor promoter, possibly a weak co-tumor-initiator when given with B[a]P, and a potent anti-tumor-initiator when given with DMBA. The anti-tumor initiating and co-tumor-initiating effects of B[e]P appear to be related to its ability to modify the conversion of the tumor initiator into an electrophilic intermediate(s) which are capable of covalently binding to DNA. In addition, B[e]P induced epidermal cellular proliferation which may be related to its promoting ability.

Original languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalCancer Letters
Volume7
Issue number1
DOIs
StatePublished - 1979
Externally publishedYes

Fingerprint

Cyclic Hydrocarbons
Benzo(a)pyrene
Carcinogens
Skin
9,10-Dimethyl-1,2-benzanthracene
Neoplasms
Papilloma
benzo(e)pyrene
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
Carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Biology

Cite this

The effects of weak or non-carcinogenic polycyclic hydrocarbons on 7, 12-dimethylbenz[a]anthracene and benzo[a]pyrene skin tumor-initiation. / Slaga, Thomas J; Jecker, L.; Bracken, W. M.; Weeks, C. E.

In: Cancer Letters, Vol. 7, No. 1, 1979, p. 51-59.

Research output: Contribution to journalArticle

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title = "The effects of weak or non-carcinogenic polycyclic hydrocarbons on 7, 12-dimethylbenz[a]anthracene and benzo[a]pyrene skin tumor-initiation",
abstract = "Benzo[e]pyrene (B[e]P) inhibited 7,12-dimethylbenz[a]anthracene (DMBA) skin tumor-initiation in mice by 84{\%}, whereas pyrene and fluoranthene inhibited DMBA initiation by 50 and 34{\%}, respectively. However, B[e]P, pyrene and fluoranthene had either no significant effect or a slight enhancing effect on benzo[a]pyrene (B[a]P) skin tumor-initiation. In addition, B[e]P had essentially no effect on the initiating ability of (±)B[a]P-7β,8α-diol-9α,10α-epoxide. As a tumor-initiator, B[e]P was found to have very weak activity at a 252 μg/level (0.4 papillomas/mouse at 40 weeks) and no activity at 100 μg. When given at a dose of 100 μg twice weekly, B[e]P induced 2.1 papillomas/mouse at 30 weeks, and 25{\%} of the mice had carcinomas at 40 weeks. However, B[e]P carcinogenic activity is weak when compared to B[a]P, which can induce a comparable tumor response at a dose of 5 μg twice weekly. When B[e]P was tested as a tumor promoter at a dose of 100 μg twice weekly after DMBA initiation, it induced 4.5 papillomas/mouse at 30 weeks and a 45{\%} carcinoma incidence at 40 weeks, which was approximately twice as effective as B[e]P alone. The data show that B[e]P is a very weak tumor initiator, a weak complete carcinogen, a moderate tumor promoter, possibly a weak co-tumor-initiator when given with B[a]P, and a potent anti-tumor-initiator when given with DMBA. The anti-tumor initiating and co-tumor-initiating effects of B[e]P appear to be related to its ability to modify the conversion of the tumor initiator into an electrophilic intermediate(s) which are capable of covalently binding to DNA. In addition, B[e]P induced epidermal cellular proliferation which may be related to its promoting ability.",
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T1 - The effects of weak or non-carcinogenic polycyclic hydrocarbons on 7, 12-dimethylbenz[a]anthracene and benzo[a]pyrene skin tumor-initiation

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AU - Weeks, C. E.

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N2 - Benzo[e]pyrene (B[e]P) inhibited 7,12-dimethylbenz[a]anthracene (DMBA) skin tumor-initiation in mice by 84%, whereas pyrene and fluoranthene inhibited DMBA initiation by 50 and 34%, respectively. However, B[e]P, pyrene and fluoranthene had either no significant effect or a slight enhancing effect on benzo[a]pyrene (B[a]P) skin tumor-initiation. In addition, B[e]P had essentially no effect on the initiating ability of (±)B[a]P-7β,8α-diol-9α,10α-epoxide. As a tumor-initiator, B[e]P was found to have very weak activity at a 252 μg/level (0.4 papillomas/mouse at 40 weeks) and no activity at 100 μg. When given at a dose of 100 μg twice weekly, B[e]P induced 2.1 papillomas/mouse at 30 weeks, and 25% of the mice had carcinomas at 40 weeks. However, B[e]P carcinogenic activity is weak when compared to B[a]P, which can induce a comparable tumor response at a dose of 5 μg twice weekly. When B[e]P was tested as a tumor promoter at a dose of 100 μg twice weekly after DMBA initiation, it induced 4.5 papillomas/mouse at 30 weeks and a 45% carcinoma incidence at 40 weeks, which was approximately twice as effective as B[e]P alone. The data show that B[e]P is a very weak tumor initiator, a weak complete carcinogen, a moderate tumor promoter, possibly a weak co-tumor-initiator when given with B[a]P, and a potent anti-tumor-initiator when given with DMBA. The anti-tumor initiating and co-tumor-initiating effects of B[e]P appear to be related to its ability to modify the conversion of the tumor initiator into an electrophilic intermediate(s) which are capable of covalently binding to DNA. In addition, B[e]P induced epidermal cellular proliferation which may be related to its promoting ability.

AB - Benzo[e]pyrene (B[e]P) inhibited 7,12-dimethylbenz[a]anthracene (DMBA) skin tumor-initiation in mice by 84%, whereas pyrene and fluoranthene inhibited DMBA initiation by 50 and 34%, respectively. However, B[e]P, pyrene and fluoranthene had either no significant effect or a slight enhancing effect on benzo[a]pyrene (B[a]P) skin tumor-initiation. In addition, B[e]P had essentially no effect on the initiating ability of (±)B[a]P-7β,8α-diol-9α,10α-epoxide. As a tumor-initiator, B[e]P was found to have very weak activity at a 252 μg/level (0.4 papillomas/mouse at 40 weeks) and no activity at 100 μg. When given at a dose of 100 μg twice weekly, B[e]P induced 2.1 papillomas/mouse at 30 weeks, and 25% of the mice had carcinomas at 40 weeks. However, B[e]P carcinogenic activity is weak when compared to B[a]P, which can induce a comparable tumor response at a dose of 5 μg twice weekly. When B[e]P was tested as a tumor promoter at a dose of 100 μg twice weekly after DMBA initiation, it induced 4.5 papillomas/mouse at 30 weeks and a 45% carcinoma incidence at 40 weeks, which was approximately twice as effective as B[e]P alone. The data show that B[e]P is a very weak tumor initiator, a weak complete carcinogen, a moderate tumor promoter, possibly a weak co-tumor-initiator when given with B[a]P, and a potent anti-tumor-initiator when given with DMBA. The anti-tumor initiating and co-tumor-initiating effects of B[e]P appear to be related to its ability to modify the conversion of the tumor initiator into an electrophilic intermediate(s) which are capable of covalently binding to DNA. In addition, B[e]P induced epidermal cellular proliferation which may be related to its promoting ability.

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