Tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland of dibenzo[a]pyrenes

the very potent environmental carcinogen dibenzo[a, l]pyrene

Ercole Cavalieri, Eleanor G Rogan, Sheila Higginbotham, Paolo Cremonesi, Shahrokh Salmasi

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112 Citations (Scopus)

Abstract

Comparative studies of tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland were conducted with several dibenzo[a]-pyrenes (DBPs). SENCAR mice were initiated with DB[a,e]P, DB[a,h]P, DB[a,i]P, DB[a,l]P and anthanthrene, and promoted with tetradecanoyl-phorbol acetate. The same compounds were tested by intramammillary injection in female Sprague-Dawley rats. Anthanthrene was inactive in both mouse skin and rat mammary gland. DB[a,e]P was a very weak tumor-initiator in mouse skin and was inactive in rat mammary gland. DB[a,h]P induced twice as many papillomas in mouse skin as DB[a,i]P, although both compounds exhibited similar tumor latencies and percentages of tumor-bearing mice. These two compounds induced similar numbers of mammary tumors, but treatment of the rats with DB[a,i]P resulted in a significantly larger number of adenocarcinomas. DB[a,l]P was toxic to both the mice and rats. Treatment of mouse skin with this compound led to an erythema, which delayed the beginning of promotion until the 3rd week after initiation. Despite this delay, papillomas began appearing 5 weeks after initiation with DB[a,l]P and the number of tumors increased rapidly. The compound was so toxic in the rats that half of the animals died in the first 9 weeks and the remaining animals were sacrificed after 15 weeks. Nonetheless, DB[a,l]P was the strongest carcinogen tested, inducing seven tumors per rat within 10 weeks. These results demonstrate that DB[a,l]P, which is present in tobacco smoke, is an extremely potent carcinogenic aromatic hydrocarbon. Furthermore, some of these compounds can serve as useful models for elucidating their mechanisms of activation.

Original languageEnglish (US)
Pages (from-to)67-72
Number of pages6
JournalJournal of Cancer Research and Clinical Oncology
Volume115
Issue number1
DOIs
StatePublished - Feb 1 1989

Fingerprint

Pyrenes
Environmental Carcinogens
Human Mammary Glands
Skin
Neoplasms
Poisons
Papilloma
Carcinogens
Inbred SENCAR Mouse
Aromatic Hydrocarbons
Erythema
dibenzo(a,l)pyrene
Smoke
Tobacco
Sprague Dawley Rats
Adenocarcinoma
Acetates
Breast Neoplasms
Injections

Keywords

  • Dibenzo[a]pyrenes
  • Mouse skin
  • Rat mammary gland
  • Tumorigenicity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{b2bc3db454da4f75837e9f6da28accd3,
title = "Tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland of dibenzo[a]pyrenes: the very potent environmental carcinogen dibenzo[a, l]pyrene",
abstract = "Comparative studies of tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland were conducted with several dibenzo[a]-pyrenes (DBPs). SENCAR mice were initiated with DB[a,e]P, DB[a,h]P, DB[a,i]P, DB[a,l]P and anthanthrene, and promoted with tetradecanoyl-phorbol acetate. The same compounds were tested by intramammillary injection in female Sprague-Dawley rats. Anthanthrene was inactive in both mouse skin and rat mammary gland. DB[a,e]P was a very weak tumor-initiator in mouse skin and was inactive in rat mammary gland. DB[a,h]P induced twice as many papillomas in mouse skin as DB[a,i]P, although both compounds exhibited similar tumor latencies and percentages of tumor-bearing mice. These two compounds induced similar numbers of mammary tumors, but treatment of the rats with DB[a,i]P resulted in a significantly larger number of adenocarcinomas. DB[a,l]P was toxic to both the mice and rats. Treatment of mouse skin with this compound led to an erythema, which delayed the beginning of promotion until the 3rd week after initiation. Despite this delay, papillomas began appearing 5 weeks after initiation with DB[a,l]P and the number of tumors increased rapidly. The compound was so toxic in the rats that half of the animals died in the first 9 weeks and the remaining animals were sacrificed after 15 weeks. Nonetheless, DB[a,l]P was the strongest carcinogen tested, inducing seven tumors per rat within 10 weeks. These results demonstrate that DB[a,l]P, which is present in tobacco smoke, is an extremely potent carcinogenic aromatic hydrocarbon. Furthermore, some of these compounds can serve as useful models for elucidating their mechanisms of activation.",
keywords = "Dibenzo[a]pyrenes, Mouse skin, Rat mammary gland, Tumorigenicity",
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