Detection of in vivo genotoxicity of endogenously formed N-nitroso compounds and suppression by ascorbic acid, teas and fruit juices.
The genotoxicity of endogenously formed N-nitrosamines from secondary amines and sodium nitrite (NaNO(2)) was evaluated in multiple organs of mice, using comet assay. Groups of four male mice were orally given dimethylamine, proline, and morpholine simultaneously with NaNO(2). The stomach, colon, liver, kidney, urinary bladder, lung, brain, and bone marrow were sampled 3 and 24 h after these compounds had been ingested. Although secondary amines and the NaNO(2) tested did not yield DNA damage in any of the organs tested, DNA damage was observed mainly in the liver following simultaneous oral ingestion of these compounds. The administration within a 60 min interval also yielded hepatic DNA damage. It is considered that DNA damage induced in mouse organs with the coexistence of amines and nitrite in the acidic stomach is due to endogenously formed nitrosamines. Ascorbic acid reduced the liver DNA damage induced by morpholine and NaNO(2). Reductions in hepatic genotoxicity of endogenously formed N-nitrosomorpholine by tea polyphenols, such as catechins and theaflavins, and fresh apple, grape, and orange juices were more effective than was by ascorbic acid. In contrast with the antimutagenicity of ascorbic acid in the liver, ascorbic acid yielded stomach DNA damage in the presence of NaNO(2) (in the presence and absence of morpholine). Even if ascorbic acid acts as an antimutagen in the liver, nitric oxide (NO) formed from the reduction of NaNO(2) by ascorbic acid damaged stomach DNA.
Ohsawa
Koh-ichi
K
Toxicology Laboratory, Taisho Pharmaceutical Co Ltd, Yoshino-cho 1-403, Kita-ku, Saitama-shi, Saitama 331-9530, Japan.
Nakagawa
Shin-ya
SY
Kimura
Masaaki
M
Shimada
Chihiro
C
Tsuda
Shuji
S
Kabasawa
Kazumi
K
Kawaguchi
Satomi
S
Sasaki
Yu F
YF
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001628:Beverages; D020552:Comet Assay; D004249:DNA Damage; D005638:Fruit; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D009025:Morpholines / Q000493:pharmacokinetics / Q000633:toxicity; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009152:Mutagenicity Tests; D009153:Mutagens; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity*; D011392:Proline / Q000493:pharmacokinetics / Q000633:toxicity; D012977:Sodium Nitrite / Q000493:pharmacokinetics / Q000633:toxicity; D013662:Tea
D009025:Morpholines; D018727:Muscarinic Antagonists; D009153:Mutagens; D009602:Nitrosamines; D013662:Tea; C032849:N,N-diamylnitrosamine; C037574:morpholine; D011392:Proline; D012977:Sodium Nitrite; D001205:Ascorbic Acid