PMID- 12189198
OWN - NLM
STAT- MEDLINE
DCOM- 20020918
LR  - 20190513
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 23
IP  - 9
DP  - 2002 Sep
TI  - Mutation, DNA strand cleavage and nitric oxide formation caused by 
      N-nitrosoproline with sunlight: a possible mechanism of UVA carcinogenicity.
PG  - 1537-40
AB  - N-Nitrosoproline (NPRO) is endogenously formed from proline and nitrite. NPRO has 
      been reported to be nonmutagenic and noncarcinogenic. In this study, we have 
      detected the direct mutagenicity of NPRO plus natural sunlight towards Salmonella 
      typhimurium. Furthermore, formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine 
      (8-oxodG), a mutagenic lesion, was observed in calf thymus DNA treated with NPRO 
      plus simulated sunlight. The treatment with NPRO and sunlight induced single 
      strand breaks in the superhelical replicative form of phage M13mp2 DNA. 
      Single-strand DNA breaks also occurred in the human fibroblast cells on treatment 
      with NPRO plus UVA, as detected by the comet assay. An analysis using scavengers 
      suggested that both reactive oxygen species and NO radical mediate the strand 
      breaks. The formation of nitric oxide was observed in NPRO solution irradiated 
      with UVA. We analyzed the photodynamic spectrum of mutation induction and DNA 
      breakage using monochromatic radiation at a series of wavelengths between 300 and 
      400 nm. Both mutation frequencies and DNA breakage were highest at the absorption 
      maximum of NPRO, 340 nm. The co-mutagenic and co-toxic actions of NPRO and 
      sunlight merit attention as possible mechanisms increasing the carcinogenic risk 
      from UVA irradiation.
FAU - Arimoto-Kobayashi, Sakae
AU  - Arimoto-Kobayashi S
AD  - Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 
      700-8530, Japan. arimoto@cc.okayama-u.ac.jp
FAU - Ando, Yoshiko
AU  - Ando Y
FAU - Horai, Yumi
AU  - Horai Y
FAU - Okamoto, Keinosuke
AU  - Okamoto K
FAU - Hayatsu, Hikoya
AU  - Hayatsu H
FAU - Lowe, Jillian E
AU  - Lowe JE
FAU - Green, Michael H L
AU  - Green MH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (DNA, Viral)
RN  - 0 (Nitrosamines)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 9007-49-2 (DNA)
RN  - 91080-16-9 (calf thymus DNA)
RN  - F8MI03SGY0 (nitrosoproline)
SB  - IM
MH  - Animals
MH  - Bacteriophages/genetics
MH  - Carcinogenicity Tests
MH  - Cattle
MH  - DNA/drug effects/metabolism/radiation effects
MH  - *DNA Damage
MH  - DNA, Viral/drug effects/metabolism/radiation effects
MH  - Mutagenicity Tests
MH  - Nitric Oxide/*metabolism
MH  - Nitrosamines/*toxicity
MH  - Salmonella typhimurium/*drug effects/genetics/radiation effects
MH  - Sunlight/adverse effects
MH  - Ultraviolet Rays/*adverse effects
EDAT- 2002/08/22 10:00
MHDA- 2002/09/19 10:01
CRDT- 2002/08/22 10:00
PHST- 2002/08/22 10:00 [pubmed]
PHST- 2002/09/19 10:01 [medline]
PHST- 2002/08/22 10:00 [entrez]
AID - 10.1093/carcin/23.9.1537 [doi]
PST - ppublish
SO  - Carcinogenesis. 2002 Sep;23(9):1537-40. doi: 10.1093/carcin/23.9.1537.