The dose dependencies of the lung carcinogenicity of 1,6-dinitropyrene (1,6-DNP) and benzo[a]pyrene (BaP) were examined by direct injections of these compounds into rat lungs. A total of 276 male F344 rats were divided into 10 groups and given various doses of 1,6-DNP or BaP, or no drug (control group). Both chemicals were injected into the lung, as suspensions in beeswax--tricaprylin and the animals were then observed for 104 weeks. The incidences of lung cancer were 0/39 (0%), 4/30 (13%), 13/31 (42%), 22/26 (85%) and 6/9 (67%) in groups treated with 0.003, 0.01, 0.03, 0.1 and 0.15 mg of 1,6-DNP respectively, and 1/29 (3%), 7/30 (23%), 22/29 (76%) and 9/13 (69%) in those treated with 0.03, 0.1, 0.3 and 1.0 mg of BaP respectively. No lung cancer was found in control rats. Thus the incidences of lung cancer induced by 1,6-DNP and BaP showed significant dose dependence. At equal doses, the incidence of lung cancer was much higher with 1,6-DNP than with BaP, and the induction of cancer by 1,6-DNP was higher even at one-third the dose of BaP. Histologically, most tumors induced by 1,6-DNP were undifferentiated neoplasms, whereas most of those induced by BaP were well-differentiated squamous cell carcinomas.

Alkanoyl-N-methylglucamides, nonionic detergents, were utilized to solubilize membrane proteins of Escherichia coli and were used to reconstitute them into liposomes. First, critical micelle concentrations (CMC) of nonanoyl-N-methylglucamide and decanoyl-N-methylglucamide were determined to be 25 mM and 7 mM, respectively, by photometric assay. Then solubilization and reconstitution of the melibiose transport carrier were performed using these detergents at concentrations above the CMC. Melibiose counterflow activity was observed with the proteoliposomes reconstituted from the extracted proteins and phospholipids. The proton-translocating ATPase complex (F1-F0) was also solubilized with these detergents. These results indicate that nonanoyl- and decanoyl-N-methylglucamide are useful detergents for solubilization and reconstitution of membrane proteins.

To investigate the modifying

The particulates in a room warmed with a radiant kerosene heater were collected, extracted and fractionated into diethyl ether‐soluble neutral, acidic and basic fractions. The mutagenicity of these fractions was measured with Salmonella typhimurium strains TA98, TA98NR, TA98/1,8‐DNP6 and TA100 in the presence and ahsence of S9 mix. Room air without the heater showed very low mutagenicity. However, a sample from a room at the beginning of the burning period showed very high mutagenicity (237 His+ revertants/plate/m*3 of air in strain TA98 in the absence of S9 mix). In contrast, emissions from the heater after it was burning stably showed low mutagenicity (9 His+ revertants/plate/m*3). The crude extract of particulates from the heater at the beginning of the burning period was analyzed by high‐pressure liquid chromatography (HPLC) and showed a considerable amount of nitropyrenes (NPs); the concentrations of 1‐NP and 1,6‐diNP were 1.62 ng and 0.149 ng/m*3 of air, respectively, and accounted for 1.2% and 17.6%, respectively, of the mutagenicity in strain TA98 in the absence of S9 mix. In addition, an HPLC‐Ames histogram showed that peaks of mutagenicity corresponding to 1‐NP and diNPs accounted for 75.7% (1‐NP, 4.9%; 1,6‐diNP, 17.1%; 1,8‐diNP, 46.3%; 1,3‐diNP, 7.4%) of the HPLC‐recovered mutagenicity for strain TA98 without S9 mix. These results suggest that kerosene heaters, especially immediately after ignition, create mutagenic substances such as NPs.

1-Nitropyrene (1-NP), a mutagenic and carcinogenic substance that occurs in the environment, is metabolized by reductive and oxidative pathways. 4,5-Epoxy,4,5-dihydro-1-NP (1-NP 4,5-oxide) and 9,10-epoxy-9,10-dihydro-1-NP (1-NP 9,10-oxide) are oxidatively activated metabolites of 1-NP, and react with glutathione. HPLC analysis of biliary metabolites from rats administered [3H]1-NP orally showed the presence of glutathione conjugates of 1-NP 4,5-oxide and 1-NP 9,10-oxide and their metabolites, cysteinylglycine and cysteine conjugates. During the 48 h following [3H]1-NP administration, 21.4% of the biliary metabolites were excreted as glutathione, cysteinylglycine and cysteine conjugates of 1-NP oxides. The proportions of glutathione conjugates of 1-NP 4,5-oxide and 1-NP 9,10-oxide were 2.6 and 10.4% respectively. Bile and pancreatic juice collected from normal rats metabolized glutathione conjugates of 1-NP oxides and produced the corresponding cysteinylglycine and cysteine conjugates. In particular, the gamma-glutamyltransferase activity of pancreatic juice was markedly high. When glutathione conjugates of 1-NP oxides were incubated with a cell-free extract of small intestinal contents, they decreased rapidly and cysteine conjugates increased via cysteinylglycine conjugates, indicating that pancreatic juice plays an important role in the small intestine for the metabolism of glutathione conjugates to corresponding cysteine conjugates. Although degradation activity of small intestinal contents for cysteine conjugates was very low, degradation activity of the contents of the cecum and large intestine was high and was inhibited by an inhibitor of cysteine conjugate beta-lyase (beta-lyase) activity, aminooxyacetic acid. Furthermore, the intestinal anaerobic bacteria Peptostreptococcus magnus and Eubacterium limosum showed high beta-lyase activity, suggesting that the cysteine conjugates might be further metabolized by beta-lyase of the normal bacterial flora in the lower intestine to the reactivated metabolites and reabsorbed.

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