Inhibitory Effect of Toluene on Tumor Promotion in Mouse Skin

Harold S. Weiss, John F. O'connell, Albert Hakaim, William T. Jacoby

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

In the two-stage mouse model for skin tumorigenesis with phorbol-12-myristate-13-acetate (PMA) as promoter, topical application of 40 μl of toluene 2X/week at the initiation/promotion site (the back) reduced the average number of tumors/mouse (ANT/M) to approximately one-fourth that of controls. Control procedure involved initiation of C3H mice with benzo[a]pyrene (BaP) and CD-1 mice with 7,12-dimethylbenz[a]anthracene (DMBA) followed by promotion with from 1 to 5 μg PMA in 40 μl acetone 2X/week. Forty microliters of toluene 2X/week per se was a weak promoter (6-13% of control ANT/M), and produced mild skin irritation at the application site but behavior and body weights were normal. The toluene inhibition of tumorigenesis was not a direct chemical action on PMA since similar effects occurred whether toluene was the vehicle for PMA or whether it was applied up to 1 day before PMA (i.e., prepromotion). Prepromotion with acetone had no effect on tumorigenesis, substantiating its use as control vehicle and suggesting that the toluene inhibition was a specific tissue reaction. The inhibitory effect appeared to be on PMA promotion rather than on initiation since toluene and acetone produced similar numbers of tumors when used as the vehicle for BaP or DMBA in two-stage or BaP in singlestage trials. The inhibition was not permanent since tumorigenesis returned to control rates 2-3 weeks after prepromotion with toluene ceased but promotion with PMA in acetone continued. Toluene may be unique among reported promotion inhibitors in that it is a widely used commercial chemical which sometimes serves as a vehicle in cancer-screening trials. Since its metabolism is reasonably well defined, it may be of value in exploring further the process of tumor promotion.

Original languageEnglish (US)
Pages (from-to)199-204
Number of pages6
JournalProceedings of the Society for Experimental Biology and Medicine
Volume181
Issue number2
DOIs
StatePublished - 1986
Externally publishedYes

Fingerprint

Toluene
Tumors
Skin
Acetates
Acetone
Neoplasms
Carcinogenesis
9,10-Dimethyl-1,2-benzanthracene
Pharmacologic Actions
Ideal Body Weight
Inbred C3H Mouse
Benzo(a)pyrene
phorbol-12-myristate
Early Detection of Cancer
Metabolism
Screening
Tissue
Inhibition (Psychology)

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Inhibitory Effect of Toluene on Tumor Promotion in Mouse Skin. / Weiss, Harold S.; O'connell, John F.; Hakaim, Albert; Jacoby, William T.

In: Proceedings of the Society for Experimental Biology and Medicine, Vol. 181, No. 2, 1986, p. 199-204.

Research output: Contribution to journalArticle

Weiss, Harold S. ; O'connell, John F. ; Hakaim, Albert ; Jacoby, William T. / Inhibitory Effect of Toluene on Tumor Promotion in Mouse Skin. In: Proceedings of the Society for Experimental Biology and Medicine. 1986 ; Vol. 181, No. 2. pp. 199-204.
@article{9cae3a77b4934abfa3547767aad14f60,
title = "Inhibitory Effect of Toluene on Tumor Promotion in Mouse Skin",
abstract = "In the two-stage mouse model for skin tumorigenesis with phorbol-12-myristate-13-acetate (PMA) as promoter, topical application of 40 μl of toluene 2X/week at the initiation/promotion site (the back) reduced the average number of tumors/mouse (ANT/M) to approximately one-fourth that of controls. Control procedure involved initiation of C3H mice with benzo[a]pyrene (BaP) and CD-1 mice with 7,12-dimethylbenz[a]anthracene (DMBA) followed by promotion with from 1 to 5 μg PMA in 40 μl acetone 2X/week. Forty microliters of toluene 2X/week per se was a weak promoter (6-13{\%} of control ANT/M), and produced mild skin irritation at the application site but behavior and body weights were normal. The toluene inhibition of tumorigenesis was not a direct chemical action on PMA since similar effects occurred whether toluene was the vehicle for PMA or whether it was applied up to 1 day before PMA (i.e., prepromotion). Prepromotion with acetone had no effect on tumorigenesis, substantiating its use as control vehicle and suggesting that the toluene inhibition was a specific tissue reaction. The inhibitory effect appeared to be on PMA promotion rather than on initiation since toluene and acetone produced similar numbers of tumors when used as the vehicle for BaP or DMBA in two-stage or BaP in singlestage trials. The inhibition was not permanent since tumorigenesis returned to control rates 2-3 weeks after prepromotion with toluene ceased but promotion with PMA in acetone continued. Toluene may be unique among reported promotion inhibitors in that it is a widely used commercial chemical which sometimes serves as a vehicle in cancer-screening trials. Since its metabolism is reasonably well defined, it may be of value in exploring further the process of tumor promotion.",
author = "Weiss, {Harold S.} and O'connell, {John F.} and Albert Hakaim and Jacoby, {William T.}",
year = "1986",
doi = "10.3181/00379727-181-42240",
language = "English (US)",
volume = "181",
pages = "199--204",
journal = "Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)",
issn = "1535-3702",
publisher = "SAGE Publications Ltd",
number = "2",

}

TY - JOUR

T1 - Inhibitory Effect of Toluene on Tumor Promotion in Mouse Skin

AU - Weiss, Harold S.

AU - O'connell, John F.

AU - Hakaim, Albert

AU - Jacoby, William T.

PY - 1986

Y1 - 1986

N2 - In the two-stage mouse model for skin tumorigenesis with phorbol-12-myristate-13-acetate (PMA) as promoter, topical application of 40 μl of toluene 2X/week at the initiation/promotion site (the back) reduced the average number of tumors/mouse (ANT/M) to approximately one-fourth that of controls. Control procedure involved initiation of C3H mice with benzo[a]pyrene (BaP) and CD-1 mice with 7,12-dimethylbenz[a]anthracene (DMBA) followed by promotion with from 1 to 5 μg PMA in 40 μl acetone 2X/week. Forty microliters of toluene 2X/week per se was a weak promoter (6-13% of control ANT/M), and produced mild skin irritation at the application site but behavior and body weights were normal. The toluene inhibition of tumorigenesis was not a direct chemical action on PMA since similar effects occurred whether toluene was the vehicle for PMA or whether it was applied up to 1 day before PMA (i.e., prepromotion). Prepromotion with acetone had no effect on tumorigenesis, substantiating its use as control vehicle and suggesting that the toluene inhibition was a specific tissue reaction. The inhibitory effect appeared to be on PMA promotion rather than on initiation since toluene and acetone produced similar numbers of tumors when used as the vehicle for BaP or DMBA in two-stage or BaP in singlestage trials. The inhibition was not permanent since tumorigenesis returned to control rates 2-3 weeks after prepromotion with toluene ceased but promotion with PMA in acetone continued. Toluene may be unique among reported promotion inhibitors in that it is a widely used commercial chemical which sometimes serves as a vehicle in cancer-screening trials. Since its metabolism is reasonably well defined, it may be of value in exploring further the process of tumor promotion.

AB - In the two-stage mouse model for skin tumorigenesis with phorbol-12-myristate-13-acetate (PMA) as promoter, topical application of 40 μl of toluene 2X/week at the initiation/promotion site (the back) reduced the average number of tumors/mouse (ANT/M) to approximately one-fourth that of controls. Control procedure involved initiation of C3H mice with benzo[a]pyrene (BaP) and CD-1 mice with 7,12-dimethylbenz[a]anthracene (DMBA) followed by promotion with from 1 to 5 μg PMA in 40 μl acetone 2X/week. Forty microliters of toluene 2X/week per se was a weak promoter (6-13% of control ANT/M), and produced mild skin irritation at the application site but behavior and body weights were normal. The toluene inhibition of tumorigenesis was not a direct chemical action on PMA since similar effects occurred whether toluene was the vehicle for PMA or whether it was applied up to 1 day before PMA (i.e., prepromotion). Prepromotion with acetone had no effect on tumorigenesis, substantiating its use as control vehicle and suggesting that the toluene inhibition was a specific tissue reaction. The inhibitory effect appeared to be on PMA promotion rather than on initiation since toluene and acetone produced similar numbers of tumors when used as the vehicle for BaP or DMBA in two-stage or BaP in singlestage trials. The inhibition was not permanent since tumorigenesis returned to control rates 2-3 weeks after prepromotion with toluene ceased but promotion with PMA in acetone continued. Toluene may be unique among reported promotion inhibitors in that it is a widely used commercial chemical which sometimes serves as a vehicle in cancer-screening trials. Since its metabolism is reasonably well defined, it may be of value in exploring further the process of tumor promotion.

UR - http://www.scopus.com/inward/record.url?scp=0022625770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022625770&partnerID=8YFLogxK

U2 - 10.3181/00379727-181-42240

DO - 10.3181/00379727-181-42240

M3 - Article

VL - 181

SP - 199

EP - 204

JO - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)

JF - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)

SN - 1535-3702

IS - 2

ER -