ABSTRACT
Epidemiological studies have shown that exposure to aflatoxin B(1) (AFB(1)) and concurrent infection with hepatitis B lead to a multiplicative risk of developing liver cancer. This chemical-viral interaction can be recapitulated in the tree shrew (Tupia belangeri chinensis). As an initial characterization of this model, the metabolism of AFB(1) in tree shrews has been examined and compared to a sensitive bioassay species, the rat. Utilizing LC/MS/MS, an unreported product, aflatoxin M(1)-N(7)-guanine (AFM(1)-N(7)-guanine), was detected in urine and hepatic DNA samples 24 h after administration of 400 microg/kg AFB(1). In hepatic DNA isolated from tree shrews, AFM(1)-N(7)-guanine was the predominant adduct, 0.74 +/- 0.14 pmol/mg DNA, as compared to 0.37 +/- 0.07 pmol/mg DNA of AFB(1)-N(7)-guanine. Conversely, in rat liver, 6.56 +/- 2.41 pmol/mg DNA of AFB(1)-N(7)-guanine and 0.42 +/- 0.13 pmol/mg DNA of AFM(1)-N(7)-guanine were detected. Rats excreted 1.00 +/- 0.21 pmol AFB(1)-N(7)-guanine/mg creatinine and 0.29 +/- 0.10 pmol AFM(1)-N(7)-guanine/mg creatinine as compared to 0.60 +/- 0.12 pmol AFB(1)-N(7)-guanine/mg creatinine and 0.69 +/- 0.16 pmol AFM(1)-N(7)-guanine/mg creatinine excreted by the tree shrew. Furthermore, tree shrew urine contained 40 times more of the hydroxylated metabolite, AFM(1), than was excreted by rats. In vitro experiments confirmed this difference in oxidative metabolism. Hepatic microsomes isolated from tree shrews failed to produce aflatoxin Q(1) or aflatoxin P(1) but formed a significantly greater amount of AFM(1) than rat microsomes. Bioassays indicated that the tree shrew was considerably more resistant than the rat to AFB(1) hepatocarcinogenesis, which may reflect the significant differences in metabolic profiles of the two species.
Subject(s)
Aflatoxin B1/administration & dosage , Aflatoxin M1/urine , Liver/chemistry , Rats, Inbred F344/urine , Tupaiidae/urine , Administration, Oral , Aflatoxin B1/adverse effects , Aflatoxin B1/urine , Aflatoxin M1/chemistry , Aflatoxin M1/metabolism , Animals , Chromatography, Liquid , DNA Adducts/biosynthesis , DNA Adducts/isolation & purification , DNA Adducts/urine , DNA Damage/drug effects , Guanine/chemistry , Guanine/metabolism , Guanine/urine , Hydroxylation , Liver/drug effects , Liver/metabolism , Male , Mass Spectrometry , Microsomes, Liver/enzymology , Models, Animal , RatsABSTRACT
Using a recently developed commercially available radioimmunoassay the concentration of the principal melatonin metabolite 6-sulfatoxymelatonin (aMT6s) in the morning urine of male tree shrews was determined. Chronic social confrontation elicited a drastic increase of aMT6s excretion in subordinate tree shrews, whereas there was a tendency to reduced excretion of the melatonin metabolite in dominant animals. These results substantiate the function of the pineal gland in transforming stimuli from the social environment to endocrine information and, therefore, are indicative for the relevant role the gland may play in the physiological reactions to chronic psychosocial stress.
Subject(s)
Arousal/physiology , Melatonin/analogs & derivatives , Pineal Gland/physiology , Social Environment , Tupaia/urine , Tupaiidae/urine , Agonistic Behavior/physiology , Animals , Dominance-Subordination , Male , Melatonin/urine , Social BehaviorABSTRACT
1. Immunoreactive androgens were measured in the urine of individual male tree-shrews throughout post-natal development. 2. Urinary androgens were low during the infantile phase and then rose significantly between the 36-45 and 46-55 day age groups, in association with the onset of pubertal development. 3. Androgen excretion increased linearly during the pubertal period in parallel with the progressive development of the testes and reproductive tract. 4. The precise endocrine correlates established in the present work suggest that serial determination of urinary androgens provides a reliable method of monitoring male reproductive development which may be applied to small, sensitive species.