CYTOCHROME-P-450 EXPRESSION IN SUDDEN-INFANT-DEATH-SYNDROME

In the human liver, the major rise of the cytochrome P-450 isoform con tent occurs during the first months following birth (e.g., the high vu lnerability period to sudden infant death syndrome (SIDS), a syndrome frequently associated with viral infection and drug hypersensitivity. We examined the expression of individual P-450 isoforms in liver sampl es collected postmortem from SIDS infants and compared values with tho se of control adults and children of the same age suffering from vario us pathologies. Hepatic microsomes were prepared and examined for thei r content in total P-450, the level of individual isoforms (CYP1A2, CY P2E1, CYP4A, CYP3A, and CYP2C) determined with specific antibodies and for their enzymatic activities. Total RNA was extracted and probed wi th several CYP cDNAs and oligomers. The overall hepatic P-450 content was not modified in SIDS infants. Among cytochrome P-450 isoforms, onl y CYP2C was markedly increased. This rise resulted from an accumulatio n of RNA encoding CYP2C and was associated with a stimulation of diaze pam demethylation. The precocious expression of CYP2C in SIDS could re sult in a higher production of epoxyeicosatrienoic acids in the neonat e, believed to act as relaxant of pulmonary smooth muscles. Its conseq uence might be the induction of fatal apnea in SIDS.