Effects of safrole and isosafrole pretreatment on N- and ring-hydroxylation of 2-acetamidofluorene by the rat and hamster

Abstract

1. The effects of safrole and isosafrole pretreatment on both N- and ring-hydroxylation of 2-acetamidofluorene were studied in male rats and hamsters. 2. Isosafrole (100mg/day per kg body wt.) pretreatment of rats for 3 days did not have any effect on urinary excretion of hydroxy metabolites of 2-acetamidofluorene. However, similar pretreatment with safrole produced increased urinary excretion of N-, 3- and 5-hydroxy derivatives. 3. Similar treatment with these two chemicals for 3 days increased ring-hydroxylation activity by rat liver microsomal material. Increases in N-hydroxylation were much less than those in ring-hydroxylation. Isosafrole was twice as effective as safrole. 4. Increases in hydroxylating activity due to safrole or isosafrole treatment were inhibited by simultaneous administration of ethionine. Similarly, ethionine inhibition was almost completely reversed by the simultaneous administration of methionine. 5. Safrole or isosafrole (0.1mm and 1mm) inhibited 7-hydroxylation activity by liver microsomal material from control rats. At 1mm these two chemicals inhibited both 5- and 7-hydroxylation activity by liver microsomal material from 3-methylcholanthrene-pretreated rats. 3-Hydroxylation activity was not inhibited by 1mm concentrations of these two chemicals. 6. A single injection of safrole (50100 or 200mg/kg body wt.) 24h before assay had no appreciable effect on either N- or ring-hydroxylation activity by hamster liver microsomal material. However, isosafrole (200mg/kg body wt.) treatment inhibited N-, 3- and 5-hydroxylation activities by hamster liver microsomal material; it had no effect on 7-hydroxylation activity.

Inhibitory effect of carbon monoxide on the N-and ring-hydroxylation of 2-acetamidofluorene by hamster hepatic microsomal preparations (Short Communication)

“…The present results, of severalfold increase in Nhydroxylation without similar increase in ringhydroxylation of 2-acetamidofluorene by liver microsomal fractions from hamsters after 3-methylcholanthrene pretreatment (Table 1), are in agreement with our previous data (Lotlikar et al, 1967;Lotlikar & Wasserman, 1972) and with those reported by .…”

Role of mixed-function amine oxidase in N-hydroxylation of 2-acetamidofluorene by hamster liver microsomal preparations

“…N-Hydroxylation of 2-acetamidofluorene by liver microsomal fractions was increased severalfold when hamsters were pretreated with 3-methylcholanthrene (Table 2). Data on the increase in Nhydroxylation are in agreement with our previous data (Lotlikar et al, 1967;Lotlikar & Wasserman, 1972) and with those reported by . Arrhenius (1968Arrhenius ( , 1969 suggested that the mixed-function amine oxidase which oxidized NN-dimethylaniline to its N-oxide was also responsible for N-oxidation of carcinogenic aromatic amines and amides.…”