Long-term outcomes of indocyanine green fluorescence imaging-guided laparoscopic lateral pelvic lymph node dissection for clinical stage II/III middle-lower rectal cancer: a propensity score-matched cohort study.

BACKGROUND: We previously reported that indocyanine green fluorescence imaging (ICG-FI)-guided laparoscopic lateral pelvic lymph node dissection (LPLND) was able to increase the total number of harvested lateral pelvic lymph nodes without impairing functional preservation. However, the long-term outcomes of ICG-FI-guided laparoscopic LPLND have not been evaluated. The aim of the present study was to compare the long-term outcomes of ICG-FI-guided laparoscopic LPLND to conventional laparoscopic LPLND without ICG-FI. METHODS: This was a retrospective, multi-institutional study with propensity score matching. The study population included consecutive patients with middle-low rectal cancer (clinical stage II to III) who underwent laparoscopic LPLND between January 2013 and February 2018. The main evaluation items in this study were the 3-year overall survival, relapse-free survival (RFS), local recurrence rate, and lateral local recurrence (LLR) rate. RESULTS: A total of 172 patients with middle-lower rectal cancer who had undergone laparoscopic LPLND were included in this study. After propensity score matching, 58 patients were matched in each of the ICG-FI and non-ICG-FI groups. There were no substantial differences in the baseline characteristics between the two groups. The ICG-FI group and non-ICG-FI group included 40 and 38 women and had a median age of 65 (IQR 60-72) and 66 (IQR 60-73) years, respectively. The median follow-up for all patients was 63.7 (IQR 51.3-76.8) months. The estimated respective 3-year overall survival, RFS, and local recurrence rates were 93.1%, 70.7%, and 5.2% in the ICG-FI group and 85.9%, 71.7%, and 12.8% in the non-ICG-FI group (p = 0.201, 0.653, 0.391). The 3-year cumulative LLR rate was 0% in the ICG-FI group and 9.3% in the non-ICG-FI group (p = 0.048). CONCLUSIONS: This study revealed that laparoscopic LPLND combined with ICG-FI was able to decrease the LLR rate. It appears that ICG-FI could contribute to improving the quality of laparoscopic LPLND and strengthening local control of the lateral pelvis. TRIALS REGISTRATION: This study was registered with the Japanese Clinical Trials Registry as UMIN000041372 ( http://www.umin.ac.jp/ctr/index.htm ).

Initial experience with the transanal approach for lateral pelvic lymph node dissection in rectal cancer.

BACKGROUND: The efficacy and safety of transanal lateral pelvic lymph node dissection (TaLPLND) in rectal cancer has not yet been clarified. The aim of the present study was to evaluate the short-term results as an initial experience of TaLPLND. METHODS: This retrospective study included patients with middle to lower rectal cancer who underwent TaLPLND from July 2018 to July 2021. Our institutions targeted lymph nodes in the internal iliac area and the obturator area for lateral pelvic lymph node dissection (LPLND). RESULTS: A total of 30 consecutive patients with rectal cancer were included in this analysis. The median age was 60 years (range, 36-83 years), and the male-female ratio was 2:1. The median operative time was 362 min (IQR, 283-661 min), and the median intraoperative blood loss was 74 ml (IQR, 5-500 ml). Intraoperative blood transfusion was required in one case. No cases required conversion to laparotomy. TaLPLND was performed bilaterally in 13 patients (43.3%). Five patients (16.7%) underwent LPLND with combined resection of the internal iliac vessels. The median distance of the distal margin from the anal verge was 20 mm. The pathological radial margin (pRM) was positive in one case, and the negative pRM rate was 96.7%. Short-term postoperative complications (Clavien-Dindo classification grade ≥ II) were observed in nine cases (30.0%). There were no cases of reoperation or mortality. The median number of harvested lateral pelvic lymph nodes was 11 (range, 3-28). On pathological examination, lateral pelvic lymph nodes were positive for metastasis in seven cases (23.3%). CONCLUSIONS: TaLPLND appeared to be beneficial from an oncological point of view because it was close to the upstream lymphatic drainage from the tumor. The short-term outcomes of this initial experience indicate that this novel approach is feasible.

Fertilizing ability of canine spermatozoa cryopreserved with skim milk-based extender in a retrospective study.

We previously reported that skim milk (SM) is an effective cryoprotectant for cryopreservation of canine spermatozoa instead of egg yolk (EY), which is the conventional cryoprotectant. In this study, the fertilizing ability and practical use of frozen canine spermatozoa prepared with SM were evaluated by transcervical insemination. Frozen-thawed spermatozoa were inseminated one to four times on days 2-9 after the LH surge. In SM group, a single transcervical insemination (TCI) on Day 5 led to higher delivery rate (83%) than any other days (33%-50%) post-LH surge. In EY group, delivery rate in double TCI on days 5 and 6 (71%) was higher compared to any other experimental groups (0%-44%). Regardless of single or double, TCI on Day 5 or Day 6 led to higher litter sizes in SM or EY groups, respectively. The breeding efficiency and litter size of single TCI on Day 5 (4.2) and double TCI on Day 5 and Day 6 (3.7) were significantly higher than in the other experimental groups in SM and EY groups, respectively (p < .05). These findings suggest that skim milk is a suitable alternative to egg yolk for cryopreservation of canine spermatozoa, and the suitable timing for insemination might be on Day 5 post-LH surge.

Responses of community structure of amoA-encoding archaea and ammonia-oxidizing bacteria in ammonia biofilter with rockwool mixtures to the gradual increases in ammonium and nitrate.

AIMS: To investigate community shifts of amoA-encoding archaea (AEA) and ammonia-oxidizing bacteria (AOB) in biofilter under nitrogen accumulation process. METHODS AND RESULTS: A laboratory-scale rockwool biofilter with an irrigated water circulation system was operated for 436 days with ammonia loading rates of 49-63 NH(3) g m(-3) day(-1). The AEA and AOB communities were investigated by denaturing gradient gel electrophoresis, sequencing and real-time PCR analysis based on amoA genes. The results indicated that changes in abundance and community compositions occurred in a different manner between archaeal and bacterial amoA during the operation. However, both microbial community structures mainly varied when free ammonia (FA) concentrations in circulation water were increasing, which caused a temporal decline in reactor performance. Dominant amoA sequences after this transition were related to Thaumarchaeotal Group I.1b, Nitrosomonas europaea lineages and one subcluster within Nitrosospira sp. cluster 3, for archaea and bacteria, respectively. CONCLUSIONS: The specific FA in circulation water seems to be the important factor, which relates to the AOB and AEA community shifts in the biofilter besides ammonium and pH. SIGNIFICANCE AND IMPACT OF THE STUDY: One of the key factors for regulating AEA and AOB communities was proposed that is useful for optimizing biofiltration technology.

Obese patients and robotic colorectal surgery: systematic review and meta-analysis.

BACKGROUND: Obesity is a major health problem, demonstrated to double the risk of colorectal cancer. The benefits of robotic colorectal surgery in obese patients remain largely unknown. This meta-analysis evaluated the clinical and pathological outcomes of robotic colorectal surgery in obese and non-obese patients. METHODS: MEDLINE, Embase, Global Health, Healthcare Management Information Consortium (HMIC) and Midwives Information and Resources Service (MIDIRS) databases were searched on 1 August 2018 with no language restriction. Meta-analysis was performed according to PRISMA guidelines. Obese patients (BMI 30 kg/m2 or above) undergoing robotic colorectal cancer resections were compared with non-obese patients. Included outcome measures were: operative outcomes (duration of surgery, conversion to laparotomy, blood loss), postoperative complications, hospital length of stay and pathological outcomes (number of retrieved lymph nodes, positive circumferential resection margins and length of distal margin in rectal surgery). RESULTS: A total of 131 full-text articles were reviewed, of which 12 met the inclusion criteria and were included in the final analysis. There were 3166 non-obese and 1420 obese patients. A longer duration of surgery was documented in obese compared with non-obese patients (weighted mean difference -21·99 (95 per cent c.i. -31·52 to -12·46) min; P < 0·001). Obese patients had a higher rate of conversion to laparotomy than non-obese patients (odds ratio 1·99, 95 per cent c.i. 1·54 to 2·56; P < 0·001). Blood loss, postoperative complications, length of hospital stay and pathological outcomes were not significantly different in obese and non-obese patients. CONCLUSION: Robotic surgery in obese patients results in a significantly longer duration of surgery and higher conversion rates than in non-obese patients. Further studies should focus on better stratification of the obese population with colorectal disease as candidates for robotic procedures.

ANTECEDENTES: La obesidad es un grave problema de salud; se ha demostrado que duplica el riesgo de cáncer colorrectal (colorectal cáncer, CRC). Los beneficios de la cirugía robótica colorrectal en pacientes obesos siguen siendo en gran medida desconocidos. Este metaanálisis evalúa los resultados clínicos y patológicos en la cirugía colorrectal robótica en pacientes obesos y no obesos. MÉTODOS: Se realizaron búsquedas bibliográficas en las bases de datos MEDLINE, EMBASE, Global Health, HMIC y MIDIRS el 1 de agosto de 2018 sin restricción de idioma. Este metaanálisis se realizó de acuerdo con las directrices PRISMA. Los pacientes obesos (IMC ≥ 30 kg/m2 ) sometidos a resecciones robóticas de CRC se compararon con pacientes no obesos. Las medidas de resultado incluidas fueron: resultados operatorios (duración de la operación, conversión a laparotomía, pérdidas hemáticas), complicaciones postoperatorias, duración de la estancia hospitalaria y resultados patológicos (número de ganglios linfáticos identificados, márgenes de resección circunferencial positivos y longitud del margen distal en la cirugía del cáncer de recto). RESULTADOS: Se revisaron 131 artículos de texto completo, de ellos, 12 artículos cumplieron los criterios de inclusión y se incluyeron en el análisis final. Hubo 3.166 pacientes no obesos y 1.420 pacientes obesos. Se registró un mayor tiempo operatorio en pacientes obesos en comparación con pacientes no obesos (diferencia media ponderada -21,989; i.c. del 95% −31,516 a 12,461, P < 0,005). Los pacientes obesos tuvieron una tasa de conversión más alta que los pacientes no obesos (i.c. del 95% 1,541 a 2,565, P < 0,005). Las pérdidas hemáticas, las complicaciones postoperatorias y la duración de la estancia hospitalaria no mostraron diferencias significativas. No hubo diferencias significativas en los resultados patológicos entre pacientes obesos y no obesos. CONCLUSIÓN: La cirugía robótica en pacientes obesos se asocia con un tiempo quirúrgico significativamente mayor y tasas de conversión más altas que en pacientes no obesos. Otros estudios deberían centrarse en estratificar mejor a los pacientes obesos con enfermedad colorrectal como candidatos a cirugía robótica.

Subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonate-enriched triglyceride oil (SUNTGA40S) in rats.

Polyunsaturated fatty acids (PUFAs), such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) are natural constituents found in human milk, fish oil or egg yolk. Until recently, infant formulas, though providing the essential fatty acid precursors for these PUFAs, did not contain preformed ARA or DHA. In this study the safety of SUNTGA40S as source of ARA, not only for use in infant formulas but also for nutritional products or food supplements, was evaluated in a subchronic study in Wistar rats, preceded by a 4-week pretreatment period of parental (F(0)) rats and exposure of the F(0) dams throughout mating, gestation and lactation. SUNTGA40S was administered at dietary levels of 0.5%, 1.5% and 5% (wt/wt) adjusted with corn oil to 5.76% added fat. An additional group received 3.65% (wt/wt) SUNTGA40S in conjunction with 2.11% (wt/wt) high DHA Tuna oil, providing an ARA:DHA ratio of 2.7:1. High-fat and low-fat controls received basal diet with or without 5.76% corn-oil supplement. The content, stability and homogeneous distribution of the test substances in the diet were confirmed under study conditions. The administration of SUNTGA40S, with or without DHA oil, did not affect health, growth, fertility or reproductive performance of the parental rats, nor pup characteristics (condition, weight gain, viability, number per litter or sex ratio). In the subchronic study with the offspring (F(1)) rats, no significant differences were found in condition, neurobehavioural observations, ophthalmoscopy, growth, urinalysis or macroscopic and microscopic findings between the test groups and the low-fat or the high-fat controls. In males of the 5% SUNTGA40S and the SUNTGA40S/DHA group, red blood cell counts, haemoglobin concentration and packed cell volume were lower and reticulocytes were slightly higher than in the high-fat and low-fat control groups. Cholesterol, triglycerides and phospholipids in plasma were lower than in the high-fat controls in both sexes in the 5% SUNTGA40S and the SUNTGA40S/DHA group and (for triglycerides only) in the 1.5% SUNTGA group. Due to the administration of extra dietary fat, food intake and prothrombin time (males only) were lower and alkaline phosphatase activity was higher in all the high-fat groups, including the corn-oil controls, as compared to the low-fat controls. The weight of the spleen was higher in males of the 5% SUNTGA40S and the SUNTGA40S/DHA group compared to both the low-fat and the high-fat controls. The effects noted in this study at high dose levels of SUNTGA40S are consistent with previously reported physiological responses to dietary intake of high PUFA containing oils. The present results provide evidence that SUNTGA40S is a safe source of arachidonic acid. Except during lactation when the intake in dams doubled, 5% Suntga40S in the diet was equivalent to an overall intake of approximately 3g/kg body weight/day in F(0) and F(1) animals.

Cloning and sequencing of a novel rat cytochrome P450 2B-encoding gene.

A novel rat P450 2B gene encoding cytochrome P450 2B15 was cloned and sequenced. The gene is separated into nine exons by eight introns. This gene structure is very similar to those of P450 2B1 and 2B2, except that the coding sequences of the gene are longer in the first and ninth exons than those of the P450 2B1 and 2B2 genes.

Molecular Analysis of Bacterial Communities in a Three-Compartment Granular Activated Sludge System Indicates Community-Level Control by Incompatible Nitrification Processes.

Bacterial community structure and the predominant nitrifying activities and populations in each compartment of a three-compartment activated sludge system were determined. Each compartment was originally inoculated with the same activated sludge community entrapped in polyethylene glycol gel granules, and ammonium nitrogen was supplied to the system in an inorganic salts solution at a rate of 5.0 g of N liter of granular activated sludge-1 day-1. After 150 days of operation, the system was found to comprise a series of sequential nitrifying reactions (K. Noto, T. Ogasawara, Y. Suwa, and T. Sumino, Water Res. 32:769-773, 1998), presumably mediated by different bacterial populations. Activity data showed that all NH4-N was completely oxidized in compartments one and two (approximately half in each), but no significant nitrite oxidation was observed in these compartments. In contrast, all available nitrite was oxidized to nitrate in compartment three. To study the microbial populations and communities in this system, total bacterial DNA isolated from each compartment was analyzed for community structure based on the G+C contents of the component populations. Compartment one showed dominant populations having 50 and 67% G+C contents. Compartment two was similar in structure to compartment one. The bacterial community in compartment three had dominant populations with 62 and 67% G+C contents and retained the 50% G+C content population only at a greatly diminished level. The 50% G+C content population from compartment one hybridized strongly with amo (ammonia monooxygenase) and hao (hydroxylamine oxidoreductase) gene probes from Nitrosomonas europaea. However, the 50% G+C content population from compartment two hybridized strongly with the hao probe but only weakly with the amo probe, suggesting that the predominant ammonia-oxidizing populations in compartments one and two might be different. Since different activities and populations come to dominate in each compartment from an identical inoculum, it appears that the nitrification processes may be somewhat incompatible, resulting in a series of sequential reactions and different communities in this three-compartment system.

Cyclin E overexpression in transitional cell carcinoma of the bladder.

We attempted to clarify the relationship between cyclin E to p27(Kip1), Ki-67 and clinicopathologic features in transitional cell bladder carcinoma. Immunohistochemical staining of archival tissue specimens of transitional cell bladder carcinoma obtained from 94 patients was performed by the labeled streptavidin-biotin-peroxidase method. Overexpression of cyclin E protein was observed in 38 of the 94 (40.4%) specimens, and was positively correlated with histological grade, Ki-67 LI and p27(Kip1) labeling index (LI). These data suggest that cyclin E may be associated with aggressive tumor growth, and may have a relationship with p27(Kip1) for the regulation of cell cycle progression in transitional cell bladder carcinoma.

Influence of carbonate on sintering of apatites.

Sintering of carbonate apatite, prepared at 100 degrees C and pH 9.0 for 3 days, was studied by thermal analysis, x-ray diffraction, and infrared spectroscopy. The sintering temperature, at which the linear thermal shrinkage of isostatically compacted specimens increased sharply, decreased in proportion to the amount of carbonate initially present in the apatite. For example, specimens with over 8 wt% carbonate could be sintered at a temperature (650 degrees C) which was nearly 400 degrees C lower than that needed for sintering a specimen with no carbonate. Amounts of carbonate lost at the end of sintering, estimated chemically and by infra-red spectroscopy, were approximately equal to sample weight losses estimated thermogravimetrically.

Small vessel pathology and coronary hemodynamics in patients with microvascular angina.

We studied the ultrastructure of cardiac myocytes and small blood vessels obtained by endomyocardial biopsy from 21 patients with microvascular angina. Ischemic ST segment depression during atrial pacing was recognised in all the patients who had normal coronary arteriograms and biopsy tissues were examined by light and electron microscopy. In patients with microvascular angina, insufficient increases in coronary sinus blood flow and in myocardial oxygen consumption measured with a Webster's catheter were apparent during atrial pacing. Biopsy samples under the light microscope showed evidence of myocardial hypertrophy and sclerosis of small arteries and arterioles with perivascular fibrosis in 18 of 19 (95%) patients. Electron microscopy revealed that many endothelial nuclei in capillaries were swollen and that lumina of small arteries and arterioles were irregularly narrowed with proliferated and deformed medial smooth muscle cells. These findings suggest that disturbances in the coronary microcirculation in these patients is responsible for the ischemic changes in electrocardiograms.

A novel skeletal drug delivery system using self-setting calcium phosphate cement. 2. Physicochemical properties and drug release rate of the cement-containing indomethacin.

A novel drug delivery device based on a self-setting bioactive cement formed from tetracalcium phosphate and dicalcium phosphate has been developed and tested in vitro with indomethacin as a model drug. Equimolar mixtures of the calcium phosphate powders containing 2 and 5% of indomethacin were transformed into a hydroxyapatite after being mixed with a dilute phosphoric acid solution. X-ray diffraction and differential scanning calorimetry results suggested that indomethacin transformed into an amorphous form in the pores of the cement matrix as it hardened. In vitro drug release from cement pellets into a 0.1 mol/L phosphate buffer at pH 7.40 and 37 degrees C continued for > 3 weeks. Release from 2 and 5% drug-loaded cements followed the Higuchi model equation. The drug release profiles of 5% drug-loaded cements with different thicknesses (0.5, 1.0, and 1.5 g) overlapped up to 90% drug release, indicating that the drug concentration gradient in the pore was independent of the thickness of the cement as expected from the model equation.

A novel skeletal drug delivery system using a self-setting calcium phosphate cement. 5. Drug release behavior from a heterogeneous drug-loaded cement containing an anticancer drug.

A novel drug delivery device based on a self-setting bioactive calcium phosphate cement formed from tetracalcium phosphate and dicalcium phosphate has been developed and tested in vitro using the anticancer agent 6-mercaptopurine (6-MP) as a model compound. X-ray diffraction results suggest that equimolar mixtures of the calcium phosphate salts were transformed into hydroxyapatite after being mixed with a dilute phosphoric acid solution, even in the presence of various amounts of 6-MP powder. The inclusion of 6-MP in the reaction mixture resulted in the formation of a homogeneous drug-containing cement. Alternatively, the drug was loaded after cement formation to produce a heterogeneous drug-containing pellet. In vitro drug release from both the homogeneous and heterogeneous drug-loaded cement pellets into simulated body fluid (pH 7.25, 37.0 degrees C) was measured using the rotating-disk method. Release from the homogeneous 5% drug-loaded cements did not obey the Higuchi equation. The release rate from the heterogeneous drug-loaded cements of different thicknesses (1, 2, and 3 mm) was a function of thickness, indicating that release kinetics could be controlled by the design of the cement formulation.

A novel skeletal drug-delivery system using self-setting calcium phosphate cement. 3. Physicochemical properties and drug-release rate of bovine insulin and bovine albumin.

A novel drug-deliver device based on a self-setting bioactive cement formed from tetracalcium phosphate and dicalcium phosphate has been developed and tested in vitro using bovine insulin and bovine albumin as model polypeptide drugs. Equimolar mixtures of the calcium phosphate powders containing bovine insulin and bovine albumin were transformed into a hydroxyapatite cement after being mixed with a dilute phosphoric acid solution. X-ray diffraction and FT-IR spectra results suggested that the raw materials transformed into lower crystallinity of hydroxyapatite as it hardened. In vitro drug release from cement pellets into a 0.1 mol/L phosphate buffer at pH 7.40 and 37 degrees C continued for more than 3 weeks. Release from the drug-loaded cements followed the Higuchi model equation.

A novel skeletal drug-delivery system using self-setting calcium phosphate cement. 4. Effects of the mixing solution volume on the drug-release rate of heterogeneous aspirin-loaded cement.

The effect of the mixing solution volume was investigated on the in vitro drug-release rate of a novel drug-delivery device based on a self-setting bioactive calcium phosphate cement containing aspirin as a model drug. Equimolar mixtures of metastable calcium phosphate powders containing various proportions (3-40 w/w %) of seed hydroxyapatite crystals transformed into hydroxyapatite after being mixed with dilute phosphoric acid. The drug release from cement pellets in vitro into a 0.1 mol/L phosphate buffer at pH 7.40 and 37 degrees C by the rotating disk method continued for more than 1 week. The drug-release rate from the cement increased with increasing volumes of mixing solution. The relationship between the liquid/powder ratio and the porosity of the cement was a straight line, indicating that the cement porosity depended on the amount of the mixing solution, but was independent of the amount of seed crystals. Drug release from the cement followed the modified Fick's law, with the rate increasing with the amount of mixing solution, since the porosity depended on the amount. The tortuosity of the cements was estimated from the modified Fick's equation, and the relationships between the drug release rate and the tortuosity of the pore in the drug-loaded cement in the plots were nonlinear. The results suggested that the drug-release rates from the cement were controlled by the drug diffusion in the pores.

Sulfite suppresses the mutagenic property of coffee.

The mutagenicity of instant and freshly brewed coffee on Salmonella typhimurium TA100 and TA98 without S9 mix was inactivated by sodium sulfite. Sulfite ion at a dose of 200 ppm almost completely inactivated the mutagenicity of coffee made in the ordinary way (5-15 mg dry weight/ml). Sodium bisulfite and potassium metabisulfite had similar effects. On the contrary, L-ascorbic acid enhanced the mutagenicity of coffee. Sodium sulfite also inactivated the phage-inducing activity of coffee in inductest III. Sodium sulfite completely suppressed the mutagenicities of 1,2-dicarbonyls, namely diacetyl and glyoxal. Diacetyl is present in coffee, beer, butter and other foods and drinks. Because sodium sulfite, sodium bisulfite and potassium metabisulfite are widely used as food additives, they should be useful in reducing the levels of mutagens in foods.

Roasting coffee beans produces compounds that induce prophage lambda in E. coli and are mutagenic in E. coli and S. typhimurium.

Freshly brewed blended coffee, instant coffee and instant caffeine-free coffee induced prophage lambda in lysogenic E. coli K12, strain GY5027. Because coffee prepared from green beans by the same extraction method as used for freshly brewed blended coffee had no prophage-inducing activity, this activity may be attributed to compounds produced in the roasting process. Roasting also produced compounds that were mutagenic in S. typhimurium TA100 and E. coli WP2 uvrA/pKM101.

Inhibition of mutagenesis by p-aminobenzoic acid as a nitrite scavenger.

Nitrite treatment enhances the direct-acting mutagenicity of various foodstuffs (e.g., chicken, bloater, the soybean flour 'kinako', and Ban-Ban-Chi sauce) on Salmonella typhimurium TA100. p-Aminobenzoic acid (PABA) and glutathione (GSH) reduced this mutagenicity; on the other hand, thioproline (TPRO) increased it. PABA seemed more effective than TPRO in scavenging nitrite ion. In analysis of the reactions of PABA and sodium nitrite under acidic conditions (pH 3.0), p-hydroxybenzoic acid (PHBA) was identified as a major reaction product. The reaction seems to involve two steps, diazotization and diazonium substitution. PHBA was not mutagenic to four strains (TA97, TA98, TA100 and TA102) of S. typhimurium with or without S9 mix.

N-2 acetylation of 2'-deoxyguanosine by coffee mutagens, methylglyoxal and hydrogen peroxide.

Coffee shows direct-acting mutagenicity in Salmonella typhimurium TA100 and most of this mutagenicity is due to the synergistic effects of methylglyoxal and hydrogen peroxide. The modifications of deoxyribonucleosides by methylglyoxal plus hydrogen peroxide were studied in vitro. When 2'-deoxyguanosine (6.25 mumole) was treated with methylglyoxal (125 mumole) and hydrogen peroxide (125 mumole) in 5 ml of 0.1 M phosphate buffer (pH 7.4) at 37 degrees C for 3 h, N2-acetyl-2'-deoxyguanosine was formed with a yield of 1.1%. Its formation increased time-dependently. By contrast, no appreciable modification of other deoxynucleosides was detected after their incubation with methylglyoxal and hydrogen peroxide under similar conditions. N2-Acetyl-2'-deoxyguanosine was also formed during incubation of 2'-deoxyguanosine with instant coffee.