Tumor-initiating activity of 4-fluoro-7,12-dimethylbenz[a]anthracene and 1,2,3,4-tetrahydro-7,12-dimethylbenz[a]anthracene in female SENCAR mice

John Digiovanni, Leila Diamond, Jody M. Singer, F. Bernard Daniel, Donald T. Witiak, Thomas J Slaga

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

We have determined the skin tumor-initiating activity in SENCAR mice of two A-ring derivatives of 7,12-dimethylbenz[a]anthracene (DMBA). 4-Fluoro-7,12-dimethyibenz[a]-anthracene at a dose of 200 nmol per mouse exhibited weak activity, producing 0.6 papillomas per mouse; doses of 10 and 20 nmol per mouse had no activity. A derivative of DMBA with the A-ring reduced, l,2,3,4-tetrahydro-7,12-dimethyl-benz[a]anthracene (1,2,3,4,-H4-DMBA), had substantial tumor-initiating activity when compared with the parent hydrocarbon. In one experiment, doses of 10 and 100 nmol per mouse gave rise to 1.6 and 9.5 papillomas per mouse, respectively; similar results were obtained in 3 additional experiments. Although the tumor-initiating activity of 1,2,3,4,-H4-DMBA was approximately one-tenth that of DMBA, this derivative was slightly (17%) more active than 3-methylcholanthrene and ∼3 times more active than benzo[a]pyrene. 1,2,3,4-H4-DMBA was tested for the ability to induce mutations to 6-thioguanine-resistance in Chinese hamster V79 cells. In the absence of feeder cells capable of metabolizing polycyclic hydrocarbons, it was not mutagenic. However, in a cell-mediated mutation assay with secondary hamster embryo cells as activators, this derivative produced mutations in a dose-dependent manner and was approximately one-tenth as active as DMBA. These results indicate that metabolism of DMBA at positions 1-, 3-, 2- and 4- is important for biological activity and that for certain derivatives (i.e., 1,2,3,4-H4-DMBA), alternate pathways of metabolic activation may also be important.

Original languageEnglish (US)
Pages (from-to)651-655
Number of pages5
JournalCarcinogenesis
Volume3
Issue number6
DOIs
StatePublished - 1982
Externally publishedYes

Fingerprint

Inbred SENCAR Mouse
9,10-Dimethyl-1,2-benzanthracene
Anthracene
Mouse
Tumors
Tumor
Derivatives
Dose
Derivative
Neoplasms
Mutation
Cell
Hydrocarbons
Papilloma
Reduced Ring
Pyrene
Bioactivity
Metabolism
Cyclic Hydrocarbons
Embryo

ASJC Scopus subject areas

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

Cite this

Tumor-initiating activity of 4-fluoro-7,12-dimethylbenz[a]anthracene and 1,2,3,4-tetrahydro-7,12-dimethylbenz[a]anthracene in female SENCAR mice. / Digiovanni, John; Diamond, Leila; Singer, Jody M.; Daniel, F. Bernard; Witiak, Donald T.; Slaga, Thomas J.

In: Carcinogenesis, Vol. 3, No. 6, 1982, p. 651-655.

Research output: Contribution to journalArticle

Digiovanni, John ; Diamond, Leila ; Singer, Jody M. ; Daniel, F. Bernard ; Witiak, Donald T. ; Slaga, Thomas J. / Tumor-initiating activity of 4-fluoro-7,12-dimethylbenz[a]anthracene and 1,2,3,4-tetrahydro-7,12-dimethylbenz[a]anthracene in female SENCAR mice. In: Carcinogenesis. 1982 ; Vol. 3, No. 6. pp. 651-655.
@article{60a67f87a8c54c75ae071664211518ae,
title = "Tumor-initiating activity of 4-fluoro-7,12-dimethylbenz[a]anthracene and 1,2,3,4-tetrahydro-7,12-dimethylbenz[a]anthracene in female SENCAR mice",
abstract = "We have determined the skin tumor-initiating activity in SENCAR mice of two A-ring derivatives of 7,12-dimethylbenz[a]anthracene (DMBA). 4-Fluoro-7,12-dimethyibenz[a]-anthracene at a dose of 200 nmol per mouse exhibited weak activity, producing 0.6 papillomas per mouse; doses of 10 and 20 nmol per mouse had no activity. A derivative of DMBA with the A-ring reduced, l,2,3,4-tetrahydro-7,12-dimethyl-benz[a]anthracene (1,2,3,4,-H4-DMBA), had substantial tumor-initiating activity when compared with the parent hydrocarbon. In one experiment, doses of 10 and 100 nmol per mouse gave rise to 1.6 and 9.5 papillomas per mouse, respectively; similar results were obtained in 3 additional experiments. Although the tumor-initiating activity of 1,2,3,4,-H4-DMBA was approximately one-tenth that of DMBA, this derivative was slightly (17{\%}) more active than 3-methylcholanthrene and ∼3 times more active than benzo[a]pyrene. 1,2,3,4-H4-DMBA was tested for the ability to induce mutations to 6-thioguanine-resistance in Chinese hamster V79 cells. In the absence of feeder cells capable of metabolizing polycyclic hydrocarbons, it was not mutagenic. However, in a cell-mediated mutation assay with secondary hamster embryo cells as activators, this derivative produced mutations in a dose-dependent manner and was approximately one-tenth as active as DMBA. These results indicate that metabolism of DMBA at positions 1-, 3-, 2- and 4- is important for biological activity and that for certain derivatives (i.e., 1,2,3,4-H4-DMBA), alternate pathways of metabolic activation may also be important.",
author = "John Digiovanni and Leila Diamond and Singer, {Jody M.} and Daniel, {F. Bernard} and Witiak, {Donald T.} and Slaga, {Thomas J}",
year = "1982",
doi = "10.1093/carcin/3.6.651",
language = "English (US)",
volume = "3",
pages = "651--655",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - Tumor-initiating activity of 4-fluoro-7,12-dimethylbenz[a]anthracene and 1,2,3,4-tetrahydro-7,12-dimethylbenz[a]anthracene in female SENCAR mice

AU - Digiovanni, John

AU - Diamond, Leila

AU - Singer, Jody M.

AU - Daniel, F. Bernard

AU - Witiak, Donald T.

AU - Slaga, Thomas J

PY - 1982

Y1 - 1982

N2 - We have determined the skin tumor-initiating activity in SENCAR mice of two A-ring derivatives of 7,12-dimethylbenz[a]anthracene (DMBA). 4-Fluoro-7,12-dimethyibenz[a]-anthracene at a dose of 200 nmol per mouse exhibited weak activity, producing 0.6 papillomas per mouse; doses of 10 and 20 nmol per mouse had no activity. A derivative of DMBA with the A-ring reduced, l,2,3,4-tetrahydro-7,12-dimethyl-benz[a]anthracene (1,2,3,4,-H4-DMBA), had substantial tumor-initiating activity when compared with the parent hydrocarbon. In one experiment, doses of 10 and 100 nmol per mouse gave rise to 1.6 and 9.5 papillomas per mouse, respectively; similar results were obtained in 3 additional experiments. Although the tumor-initiating activity of 1,2,3,4,-H4-DMBA was approximately one-tenth that of DMBA, this derivative was slightly (17%) more active than 3-methylcholanthrene and ∼3 times more active than benzo[a]pyrene. 1,2,3,4-H4-DMBA was tested for the ability to induce mutations to 6-thioguanine-resistance in Chinese hamster V79 cells. In the absence of feeder cells capable of metabolizing polycyclic hydrocarbons, it was not mutagenic. However, in a cell-mediated mutation assay with secondary hamster embryo cells as activators, this derivative produced mutations in a dose-dependent manner and was approximately one-tenth as active as DMBA. These results indicate that metabolism of DMBA at positions 1-, 3-, 2- and 4- is important for biological activity and that for certain derivatives (i.e., 1,2,3,4-H4-DMBA), alternate pathways of metabolic activation may also be important.

AB - We have determined the skin tumor-initiating activity in SENCAR mice of two A-ring derivatives of 7,12-dimethylbenz[a]anthracene (DMBA). 4-Fluoro-7,12-dimethyibenz[a]-anthracene at a dose of 200 nmol per mouse exhibited weak activity, producing 0.6 papillomas per mouse; doses of 10 and 20 nmol per mouse had no activity. A derivative of DMBA with the A-ring reduced, l,2,3,4-tetrahydro-7,12-dimethyl-benz[a]anthracene (1,2,3,4,-H4-DMBA), had substantial tumor-initiating activity when compared with the parent hydrocarbon. In one experiment, doses of 10 and 100 nmol per mouse gave rise to 1.6 and 9.5 papillomas per mouse, respectively; similar results were obtained in 3 additional experiments. Although the tumor-initiating activity of 1,2,3,4,-H4-DMBA was approximately one-tenth that of DMBA, this derivative was slightly (17%) more active than 3-methylcholanthrene and ∼3 times more active than benzo[a]pyrene. 1,2,3,4-H4-DMBA was tested for the ability to induce mutations to 6-thioguanine-resistance in Chinese hamster V79 cells. In the absence of feeder cells capable of metabolizing polycyclic hydrocarbons, it was not mutagenic. However, in a cell-mediated mutation assay with secondary hamster embryo cells as activators, this derivative produced mutations in a dose-dependent manner and was approximately one-tenth as active as DMBA. These results indicate that metabolism of DMBA at positions 1-, 3-, 2- and 4- is important for biological activity and that for certain derivatives (i.e., 1,2,3,4-H4-DMBA), alternate pathways of metabolic activation may also be important.

UR - http://www.scopus.com/inward/record.url?scp=0019933638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019933638&partnerID=8YFLogxK

U2 - 10.1093/carcin/3.6.651

DO - 10.1093/carcin/3.6.651

M3 - Article

C2 - 6811143

AN - SCOPUS:0019933638

VL - 3

SP - 651

EP - 655

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 6

ER -