Stability of Terpenoid-Derived Secondary Ozonides in Aqueous Organic Media.

1,2,4-Trioxolanes, known as secondary ozonides (SOZs), are key products of ozonolysis of biogenic terpenoids. Functionalized terpenoid-derived SOZs are readily taken up into atmospheric aerosols; however, their condensed-phase fates remain unknown. Here, we report the results of a time-dependent mass spectrometric investigation into the liquid-phase fates of C10 and C13 SOZs synthesized by ozonolysis of a C10 monoterpene alcohol (α-terpineol) in water:acetone (1:1 = vol:vol) mixtures. Isomerization of Criegee intermediates and bimolecular reaction of Criegee intermediates with acetone produced C10 and C13 SOZs, respectively, which were detected as their Na+-adducts by positive-ion electrospray mass spectrometry. Use of CD3COCD3, D2O, and H218O solvents enabled identification of three types of C13 SOZs (aldehyde, ketone, and lactol) and other products. These SOZs were surprisingly stable in water:acetone (1:1) mixtures at T = 298 K, with some persisting for at least a week. Theoretical calculations supported the high stability of the lactol-type C13 SOZ formed from the aldehyde-type C13 SOZ via intramolecular rearrangement. The present results suggest that terpenoid-derived SOZs can persist in atmospheric condensed phases, potentially until they are delivered to the epithelial lining fluid of the pulmonary alveoli via inhaled particulate matter, where they may exert hitherto unrecognized adverse health effects.

Novel mutations of neurofibromatosis type 1 gene in small cell lung cancers.

PURPOSE: Mutations in the GTPase-activating protein-related domain (GRD) of the von Recklinghausen neurofibromatosis type 1 (NF1) gene have been reported in several tumors that were not previously associated with NF1. We analyzed 37 cases of lung cancer, including 9 cases of small cell carcinoma, to detect mutations in this domain. METHODS: DNA was extracted from the tumors, and single-strand conformation polymorphism and direct sequencing were used to detect mutations. RESULTS: Three cases of small cell carcinoma had mutations in NF1-GRD. There were two incidences of an A --> G transition at the second base of codon 1415 resulting in Glu --> Gly substitution, and one incidence of an A --> G transition at the third base of codon 1411 (Pro) without amino acid substitution. All three patients had both hilar and mediastinal lymphatic metastasis. CONCLUSIONS: A mutation in this region could imply a poor prognosis.