Many nutritional, hormonal, and environmental factors affect carcinogenesis
and growth of established tumors in rodents. In some cases, these factors
may either enhance or attenuate the neoplastic process. Recent experiments
performed in our laboratory using tissue-isolated rat hepatoma 7288CTC in v
ivo or during perfusion in. situ have demonstrated new interactions among f
our of these factors. Two agents, dietary linoleic acid (C18:2n6) and "ligh
t at night," enhanced tumor growth, and two others, melatonin and n3 fatty
acids, attenuated growth. Linoleic acid stimulated tumor growth because it
is converted by hepatoma 7288CTC to the mitogen, 13-hydroxyoctadecadienoic
acid (13-HODE). Melatonin, the neurohormone synthesized and secreted at nig
ht by the pineal gland, and dietary n3 fatty acids are potent antitumor age
nts. Both inhibited tumor linoleic acid uptake and 13-HODE formation. Artif
icial Light, specifically "light at night," increased tumor growth because
it suppressed melatonin synthesis and enhanced 13-HODE formation. Melatonin
and n3 fatty acids acted via similar or identical Gi protein-coupled signa
l transduction pathways, except that melatonin receptors and putative n3 fa
tty acid receptors were used. The results link the four factors in a common
mechanism and provide new insights into the roles of dietary n6 and n3 pol
yunsaturated fatty acid intake, "light at night," and melatonin in cancer p
revention in humans. (C) 2001 Elsevier Science Inc. All rights reserved.