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Title: EFFECT OF NATURALLY OCCURRING COUMARINS ON THE FORMATION OF EPIDERMAL DNA ADDUCTS AND SKIN TUMORS INDUCED BY BENZO(A)PYRENE AND 7,12-DIMETHYLBENZ(A) ANTHRACENE IN SENCAR MICE

Author
item CAI, YINGNA - UNIV TEXAS M.D. ANDERSON
item JOHNSON, DENNIS - UNIV TEXAS M.D. ANDERSON
item DUBOWSKI, ADAM - UNIV TEXAS M.D. ANDERSON
item BOSTIC, SAMANTHA - UNIV TEXAS M.D. ANDERSON
item Ivie, Glen - Wayne
item DIGIOVANNI, JOHN - UNIV TEXAS M.D. ANDERSON

Submitted to: Carcinogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/13/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: Living plants often contain a number of chemicals that are not necessary for the nutrition of the plant but which are present for various reasons, including protecting the plants from insects or other animals that would otherwise eat them, or protecting them from diseases such as viruses and molds. Many plants, including plants such as celery, parsnip, and parsley, ,contain a group of chemicals known as furanocoumarins which are thought to be distasteful or toxic to insects and certain plant diseases. Although humans eats these plants, the levels of furanocoumarins in them are low enough such that they are not normally harmful. We have now found that certain of these furanocoumarins have another interesting effect in mammals. In certain mouse cancer models, some furanocoumarins act to delay the onset of cancer and thus seem to have a protective effect against cancer. These studies do not mean that furanocoumarins act in humans to reduce the incidence of cancer or slow down the cancer process, but they d point out an interesting and potentially significant action by furanocoumarins that further study may show to have significant health-related effects in people.

Technical Abstract: Several naturally occurring coumarins previously found to be potent inhibitors of mouse hepatic ethoxyresorufin-O-deethylase (EROD) and/or pentoxyresorufin-O-dealkylase (PROD) were examined for their effects on formation of benzo[a]pyrene (B[a]P) and 7,12-dimethylbenz[a]anthracene (DMBA) DNA adducts in mouse epidermis, as well as, their effects on skin tumor initiation by these polycyclic aromatic hydrocarbons (PAH). Bergamottin, a potent inhibitor of hepatic EROD, given topically 5 min prior to an initiating dose of B[a]P, significantly decreased total covalent binding of B[a]P to DNA in a dose-dependent manner 24 h after treatment. A dose of 400 nmol bergamottin reduced covalent binding of B[a]P by 72%. Coriandrin, at a dose of 400 nmol also significantly reduced total covalent binding of B[a]P by 59%. In addition, formation of the major(+)anti-B[a]P-diol epoxide-N**2-dGuo adduct was selectively reduced by yboth of these coumarins. In contrast, bergamottin and coriandrin did not significantly decrease covalent binding of DMBA to epidermal DNA at doses of either 400 nmol or 800 nmol. Imperatorin and isopimpinellin, which are more potent inhibitors of hepatic PROD activity, significantly reduced overall binding of DMBA to epidermal DNA by 67% and 52%, respectively, when applied at doses of 400 nmol. These two coumarins also inhibited B[a]P-DNA adduct formation at similar doses bu to a lesser extent. Imperatorin at a dose of 400 nmol dramatically decreased formation of covalent DNA adducts derived from both the anti and syn diol epoxides of DMBA. Bergamottin was a potent inhibitor of tumor initiation by B[a]P while coriandrin was less effective in this regard.