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Enhanced neoplastic growth and metabolism have been reported in animals maintained in a constant light (24L:0D) environment. Results from this laboratory indicate that tumor growth is directly dependent upon increased ambient blood concentrations of arachidonic and linoleic acids, particularly linoleic acid. Tumor linoleic acid utilization and production if its putative mitogenic metabolite, 13hydroxyoctadecadienoic acid (13-HODE), are suppressed by the circadian neurohormone melatonin, the production of which is itself regulated by light in all mammals. This study was performed to determine whether minimal light contamination (0.2 lux) in an animal room during an otherwise normal dark phase may disrupt normal circadian production of melatonin and affect tumor growth and metabolism. Animals of groups I (12L:12D), II (12L:12-h light-contaminated dark phase), and III (24L:0D) had plasma total fatty acid (TFA), linoleic acid (LA), and melatonin concentrations measured prior to tumor implantation; groups I and II had daily cycles in plasma TFA and LA values, whereas group III had constant values throughout the day. The integrated mean TFA and LA values for the entire day were similar in all groups. Although group-I animals had a normal nocturnal surge of melatonin (127.0 pg/ml) at 2400 h, the nocturnal amplitude was suppressed in group-II animals (16.0 pg/ml); circadian variation in melatonin concentration was not seen in group-III animals (7.4 pg/ml). At 12 weeks of age, rats had the Morris hepatoma 7288CTC implanted as “tissue-isolated” tumors grown subcutaneously. Latency to onset of palpable tumor mass for groups I, II, and III was 11, 9, and 5 days respectively. Tumor growth rates were 0.72 ± 0.09, 1.30 ± 0.15, and 1.48 ± 0.17 g/d (mean ± SD, n = 6/group) in groups I, II, and III respectively. Arteriovenous difference measurements for TFA and LA across the tumors were 4.22 ± 0.89 and 0.83 ± 0.18 (group I), 8.26 ± 0.66 and 1.64 ± 0.13 (group II), and 7.10 ± 0.78 and 1.50 ± 0.16 (group III) /min/g, and groups II and III were significantly different from group I (P < 0.05). Tumor TFA and LA contents were 14.3 ± 1.7 and 1.8 ± 0.3 (group I), 52.9 ± 5.5 and 7.9 ± 0.8 (group II), and 106.0 ± 12.0 and 18.5 ± 2.4 (group III) g/g and were significantly different from each other (P < 0.001). Production of 13-HODE by the hepatomas in groups I, II, and III was 35.5 ± 6.3, 109.6 ± 10.6, and 196.2 ± 34.9 ng/min/g respectively, values which also were significantly different among groups (P < 0.001). The results indicate that minimal light contamination of only 0.2 lux during an otherwise normal dark phase inhibits host melatonin secretion and increases the rate of tumor growth and lipid uptake and metabolism. These data suggest that great care must be taken to prevent “light-leaks” in animal rooms during the dark phase of a diurnal cycle because such contamination may adversely affect the outcome of tumor growth investigations.
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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