TRANSMETHYLATION REACTIONS AND AUTORADIOGRAPHIC DISTRIBUTION OF VITAMIN-B-12 - EFFECTS OF CLIOQUINOL TREATMENT IN MICE

The catastrophic epidemic of subacute myelo-optic neuropathy (SMON) af fected Japan around 1970 with thousands of victims. The cause was attr ibuted to high doses of locally acting oxyquinolines. It has been spec ulated that oxyquinoline derivatives of the clioquinol type can distur b the retention of vitamin Bit through chelation of Co2+. In the prese nt paper, possible effects of clioquinol on the uptake and tissue dist ribution of [Co-57]-cyanocobalamin have been studied in mice. In vivo experiments showed markedly decreased accumulation of radiolabelled vi tamin Bit in the kidney and skin in animals that were pre-treated with clioquinol. The chloroform:water partition coefficients for [Co-57]-c yanocobalamin in the presence or absence of clioquinol were also deter mined. No statistically significant alterations in the partition coeff icient for [Co-57] -cyanocobalamin in the presence of clioquinol was e vident, indicating that clioquinol does not bind cobalt. In addition, transmethylation reactions in the CNS in mice treated with clioquinol were studied. Specific activities of methionine adenosyltransferase, a nd S-adenosylhomocysteine levels were not affected. In contrast, clioq uinol treatment caused a significant increase in the levels of S-adeno sylmethionine in the brain. The data of the present study show that cl ioquinol treatment can affect the accumulation of vitamin B-12 in the kidney and the skin but not in the brain. These results do not support the hypothesis that clioquinol causes its damage to the nervous syste m by a direct chemical interaction with vitamin B-12.