Research Section Direct and Translactational Eect of Arecoline Alkaloid on the Clocimum Oil-modulated Hepatic Drug Metabolizing Enzymes in Mice A. SINGH *, S. P. SINGH and R. BAMEZAI Human Genetics Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India (Accepted 1 November 1999) AbstractÐThe present study assesses the potential of arecoline alkaloid, by direct exposure in lactating dams and translactational exposure in neonates, to modulate the ecacy of clocimum oil as a blocking agent in chemopreventive pathway. Clocimum oil (25 or 50 l/dam/day) induced a signi®cant increase in the hepatic levels of phase II glutathione S-transferase (GST) and acid-soluble sulfhydryl in lactating dams and suckling neonates while the elevated levels of hepatic phase I cytochrome b5 (Cyt. b5) and cytochrome P-450 (P450) were observed only in the dams. Arecoline (0.6 mg/dam/day) alone did not modulate the hepatic GST and sulfhydryl levels in either dams or pups, although signi®cant induction was observed in the hepatic levels of Cyt. b5, P450 and malondialdehyde (MDA) in lactating dams and suckling neonates. Clocimum oil-modu- lated hepatic levels of phase II components were depressed whereas phase I enzymes and lipid peroxides levels were further elevated by clocimum oil-plus-arecoline treatment. The direct or translactationally augmented levels of bioactivated species of the administered compounds, via enhanced phase I oxidative catalysis and less ecient GST/GSH conjugational detoxication, may suggest the antagonistic in¯uence of arecoline on che- mopreventive ecacy of clocimum oil. # 2000 Elsevier Science Ltd. All rights reserved Keywords: arecoline; clocimum oil; drug metabolizing enzymes; lactating dams; neonates. Abbreviations: BSA=bovine serum albumin; CDNB=1-chloro-2,4-dinitrobenzene; GSH=glutathione; GST= glutathione S-transferase; MDA= malondialdehyde. INTRODUCTION Chemoprevention of cancer involves the preventive intervention trials of non-cytotoxic and pharmaco- logical agents with signi®cant and plausible biologi- cal activity in animals, in vitro and short-term human studies (Sharma et al., 1994; Wattenberg, 1992). The chemopreventive potential of a wide range of non- nutrients (Wattenberg, 1992), micronutrients (Moon and Micozzi, 1988) and macronutrients (Micozzi and Moon, 1992) has been correlated with their capa- city to modulate the competing pathways of drug- metabolizing system enzymes which play an impor- tant role in their bioactivation and conjugational detoxication. The biochemical modulation of phase I and phase II enzymes of the drug-metabolizing sys- tem thus provides a practical approach to identify chemopreventors as agents to prevent, halt or reverse the process of chemical carcinogenesis besides oer- ing a means to study the mechanism of carcinogen- esis (Wattenberg, 1992). Clocimum oil, an eugenol rich (85±90%) oil, is extracted from the polycross hybrid strain of Oci- mum gratissimum developed by Regional Research Laboratory, Jammu (India). Recent work in our and several other laboratories has revealed the anti- carcinogenic (Singh et al., 1999) antimutagenic (Oba- seiki-Ebor et al., 1993), immunomodulatory (Atal et al., 1986) and radioprotective (Ganasoundari et al., 1997) potential of clocimum oil and its originator plant Ocimum. Eugenol (1-allyl-4-hydroxy-3-meth- oxybenzene), the active principle of clocimum oil, is also reported for the signi®cant antioxidant (Kumaravelu et al., 1995), anti-genotoxic (Rompel- berg et al., 1996) and hepatoprotective (Nagababu et 0278-6915/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved. Printed in Great Britain PII: S0278-6915(00)00045-4 Food and Chemical Toxicology 38 (2000) 627±635 www.elsevier.com/locate/foodchemtox *Corresponding author. Fax: 215-923-7144.