Suppression of Mammary Carcinogenesis Through Early Exposure to Dietary Lipotropes Occurs Primarily In Utero

• Published in: Nutrition and cancer 2015-11, Vol.67 (8), p.1278-1284
• Main Authors: Mabasa, Lawrence, Cho, Kyongshin, Choi, Woo-Sik, Crane, Courtney L, Cho, Kwangbog, Singh, Raushan K, Park, Chung S
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; body weight; Breastfeeding & lactation; carcinogenesis; Carcinogens; choline; Choline - administration & dosage; chromatin; Chromatin Assembly and Disassembly - drug effects; Diet; dietary exposure; enzyme activity; Female; females; folic acid; Folic Acid - administration & dosage; Food fortification; histone deacetylase; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Lactation; mammary neoplasms (animal); Mammary Neoplasms, Animal - chemically induced; Mammary Neoplasms, Animal - enzymology; Mammary Neoplasms, Animal - prevention & control; maternal effect; Maternal-Fetal Exchange; methionine; Methionine - administration & dosage; Methylnitrosourea - administration & dosage; Oncology; Pregnancy; progeny; pups; Rats; Rats, Sprague-Dawley; Rodents; Vitamin B; Vitamin B 12 - administration & dosage; vitamin B12
• ISSN: 1532-7914; 0163-5581; 1532-7914
• DOI: 10.1080/01635581.2015.1087039

The study determined whether feeding during lactation affects the suppressive effect of maternal dietary lipotropes (i.e., methionine, choline, folate, and vitamin B ₁₂) on mammary carcinogenesis. Pregnant Sprague-Dawley rats were randomly allocated to the control diet during pregnancy and lactation (CC), lipotropes-fortified diet during pregnancy (LC), lipotropes-fortified diet during pregnancy plus lactation (LL), or lipotropes-fortified diet during lactation (CL). Randomly selected female offspring from each group were injected intraperitoneally with 50 mg/kg body weight of N -nitroso- N -methylurea at 50 days of age to induce mammary tumors. The LC and LL diets significantly increased tumor latency and survival (P < 0.05). Tumor volumes were significantly suppressed in LC and LL offspring as compared with the CC and CL pups (3759.1 ± 563.0 and 3603.7 ± 526.1 vs. 7465.0 ± 941.1 and 5219.3 ± 759.8 mm ³, respectively; P < 0.05). Both LC and LL lowered tumor multiplicity as compared with CC and CL (P < 0.05). The LC and LL diets repressed transcription of histone deacetylase (HDAC) 1 as well as total HDAC enzyme activity as compared with CC and CL diets (P < 0.05). Data suggest that the tumor suppressive effect of maternal dietary lipotropes is primarily in utero and may be linked to regulation of proteins involved in chromatin remodeling.