title: Chemoprevention of mammary carcinogenesis by hydroxylated derivatives of d-limonene.
abstract: The monoterpene d-limonene has been shown to an effective, non-toxic chemopreventive agent in mammary and other rodent tumor models. The studies reported here investigated structure-activity relationships among limonene and three hydroxylated derivatives in the prevention of dimethylbenz[a]anthracene (DMBA)-induced mammary cancer. Rats were fed control or 1% limonene, carveol, uroterpenol or sobrerol diets from 2 weeks before to one week after carcinogen administration. Carveol, uroterpenol and sobrerol significantly prolonged tumor latency and decreased tumor yield. Sobrerol was the most potent of the monoterpenes tested, decreasing tumor yield to half that of the control, a level previously achieved with 5% limonene diets. Excretion of radioactivity from [3H]DMBA was doubled in rats fed 5% limonene and nearly tripled in rats fed 1% sobrerol. Sobrerol is thus 5-fold more potent than limonene in both enhancing carcinogen excretion and in preventing tumor formation. These data demonstrate that hydroxylation of monoterpenes affects chemopreventive potential, with 2 hydroxyl groups greater than 1 greater than 0. Sobrerol, carveol and uroterpenol are novel cancer chemopreventive agents with little or no toxicity.
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison 53792.
authors.forename: P L
authors.initials: PL
authors.lastname: Crowell
authors.forename: W S
authors.initials: WS
authors.lastname: Kennan
authors.forename: J D
authors.initials: JD
authors.lastname: Haag
authors.forename: S
authors.initials: S
authors.lastname: Ahmad
authors.forename: E
authors.initials: E
authors.lastname: Vedejs
authors.forename: M N
authors.initials: MN
authors.lastname: Gould
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes; D005260:Female; D006900:Hydroxylation; D000077222:Limonene; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D039821:Monoterpenes; D051381:Rats; D011920:Rats, Inbred WF; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes; D039821:Monoterpenes; D013729:Terpenes; D015127:9,10-Dimethyl-1,2-benzanthracene; C013593:4-menth-1-ene-8,9-diol; C075856:carveol; D000077222:Limonene; C003316:sobrerol