Inhibiting effects of nicotinamide on urethane-induced malformations and tumors in mice.
The antipellagratic vitamin, nicotinamide, significantly suppressed urethane-induced malformations, when it was given intraperitoneally to pregnant JCL:ICR mice immediately after a single subcutaneous injection of urethane (1.0 mg/g) on the 9th day of gestation. The level of inhibition increased with the doses of nicotinamide: 33.0, 55.8, and 70.0% at doses of 0.1, 0.3, and 0.5 mg/g, respectively. Polydactyly and tail anomalies were markedly suppressed by the post-treatment with nicotinamide, while cleft palates were less effectively suppressed. Nicotinamide was still effective, when it was given during the period of 24-48 h after urethane treatment. Furthermore, dietary administration of nicotinamide also reduced urethane-induced malformations. The level of inhibition was 39.4 and 61.1% at 0.5 and 1.0% of nicotinamide in the diet, respectively. Higher doses of nicotinamide (3 and 5% in diet) also inhibited urethane-induced malformations, but not so effectively as lower doses. The inhibiting effects of nicotinamide on the spontaneous incidence of cleft lips and palates in CL/Fr mice were significant at a low dose (0.5% in diet), but not at a higher dose (1.0%). When [carbonyl-14C]nicotinamide was given to pregnant mice, nicotinamide and small amounts of nicotinamide adenine dinucleotide (NAD+), but not nicotinic acid, were detected chromatographically in the fetus and placenta, indicating that nicotinamide or NAD+ acts directly on the fetus to suppress urethane-induced malformations. A preliminary study revealed that urethane-induced lung tumorigenesis in JCL:ICR mice was also inhibited by post-treatment with nicotinamide in the diet. The level of inhibition was proportional to the dose of nicotinamide, that is, 35.0 and 62.8% at 1.0 and 2.5% of nicotinamide in the diet, respectively.
Gotoh
H
H
Department of Life Science, Saho Women's College, Nara, Japan.
Nomura
T
T
Nakajima
H
H
Hasegawa
C
C
Sakamoto
Y
Y
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D002971:Cleft Lip / Q000517:prevention & control; D002972:Cleft Palate / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D005260:Female; D008175:Lung Neoplasms / Q000139:chemically induced; D008431:Maternal-Fetal Exchange; D051379:Mice; D009536:Niacinamide / Q000378:metabolism / Q000494:pharmacology*; D011247:Pregnancy; D013723:Teratogens / Q000037:antagonists & inhibitors; D014520:Urethane / Q000037:antagonists & inhibitors*
D013723:Teratogens; D009536:Niacinamide; D014520:Urethane