HISTOLOGICAL LOCALIZATION OF MESSENGER-RNAS FOR RAT ACETYLTRANSFERASES THAT ACETYLATE SEROTONIN AND GENOTOXIC ARYLAMINES

Rat acetyltransferases (ATs) can acetylate the endogenous arylalkylami nes tryptamine, 5-hydroxytryptamine (serotonin), and 5-methoxytryptami ne, the immediate precursor of melatonin. The same enzymes also acetyl ate and activate exogenous, carcinogenic arylamines, thereby being imm ediately responsible for the generation of DNA adducts. Localization o f AT transcripts in the pineal gland and in specific cells of the inte stine, cerebral cortex, pituitary, and lung identifies cells that may be important to the neurotransmitter and hormonal roles of the tryptam ine derivatives. Transcript localization in liver, mammary gland, Zymb al gland, kidney, forestomach, and bladder, as well as intestine and l ung, identifies cells that may be at increased carcinogenic risk becau se they can convert N-hydroxylated arylamines to genotoxic metabolites . Highly specific expression is also observed in the reproductive orga ns of both the male and female, including the testes, epididymis, uter us, ovary, and fallopian tube. In addition to these diverse organs, wh ich are consistent with possible roles of the enzyme in carcinogen met abolism, neurotransmission, or hormonal regulation, specific cells of the cornea, cilliary process of the eye, olfactory process, adrenal gl and, exorbital lacrimal gland, and skin also exhibit highly specific e xpression of AT mRNAs for which one can only speculate as to their fun ction, In virtually every case, the extent of labeling suggested that AT1 was expressed at levels that were orders of magnitude higher than those of AT2. Qualitative differences in the sites of mRNA of these tw o enzymes were seen only in the olfactory process, in which AT1 was ex pressed in both respiratory and olfactory epithelia as well as Bowman' s cells, and AT2 was detected only in the latter cells. The available data support the conclusion that the ATs are likely to be involved bot h in the metabolic activation of exogenous carcinogenic amines as well as the metabolism of endogenous arylalkylamines that play important h ormonal and neurotransmitter roles.