• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 국제심포지움
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• pp.1-19
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• 2002

It is well established that the initiating event in chemical carcinogenesis is the binding of reactive carcinogens to DNA. Thus, a number of analytic methods have been developed for determining levels of carcinogen-DNA adducts in humans as a marker of individual exposure and, potentially, of risk for cancer development. In addition, reactive carcinogens also bind to protein suggesting protein adducts can be used as a surrogate for DNA adducts in some situations. We have developed monoclonal and polyclonal antibodies to carcinogen-DNA and protein adductis and highly sensitive ELISA and immunohistochemical assays for determining levels of adducts in human tissues. These studies have demonstrated higher levels of adducts in those with higher exposure as a result of workplace, dietary, chemotherapy, environmental of lifestyle (smoking) exposures. Elevated levels of adducts have been found in lung and liver cancer cases compared to controls. We have also used DNA adducts to determine efficacy of an antiosidant vitamin intervention. DNA adduct studies have demonstrated very different levels of damage in those with similar exposure levels. These interindividual differences are likely the result genetic differences in capacity to activate carcinogens, detoxify reactive intermediates and repair DNA adducts once formed. We are currently investigating the relationship between polymorphisms in a number of these genes to determine their relationship to adduct levels as well as their ability to confer increased risk for cancer development. The ability to identify high risk individuals will allow the targeting of screening and preventive strategies to those most likely to benfit.

• 한국산업보건학회지
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• 제10권2호
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• pp.124-139
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• 2000

This study was performed to investigate monoacetylbenzidine(MABZ) and benzidine(BZ) hemoglobin adducts among workers who worked at benzidine based dye manufacturing company, and exposed by benzidine and benzidine based dye. The hemoglobin adducts were compared with work environment assessment result for evaluating the usefulness of biological monitoring. The mean BZ hemoglobin adducts among the first synthesis worker's hemoglobin adducts were $40.69{\mu}gBZ/g$ Hb and those of dry and packing workers were $22.14{\mu}gBZ/g$ Hb. The mean of MABZ hemoglobin adducts among 1st synthesis workers were $255.84{\mu}gMABZ/g$ Hb, dispersion worker's hemoglobin adducts were $76.17{\mu}gMABZ/g$ Hb and synthesis worker's hemoglogin adducts were $28.66{\mu}gMABZ/g$ Hb. Work environment assessment results during past 3 years were $0.0065mg/m^3$ and $0.5659mg/m^3$ of benzidine based dye concentration in ambient air of drying and packing only. Dye producing process was categorized by the possibility of exposure to benzidine and benzidine based dye. BZ and MABZ hemoglobin adducts were $19.55{\mu}gBZ/g$ Hb, $119.80{\mu}gMABZ/g$ Hb among workers who exposed by benzidine dihydrochloride and $16.32{\mu}gBZ/g$ Hb, $316.56{\mu}gMABZ/g$ Hb among workers who exposed by benzidine based dye. BZ hemoglobin adducts were not detected among control group and MABZ hemoglobin adducts were $5.33{\mu}gMABZ/g$ Hb. The differences between control and other exposed group was statistically significant. But there was no statistically significant differences between benzidine dihydrochloride exposed process and benzidine based dye exposed group. BZ and MABZ hemoglobin adducts were $2.23{\mu}gBZ/g$ Hb, $76.17{\mu}gMABZ/g$ Hb and $3.46{\mu}gBZ/g$ Hb, $21.33{\mu}gMABZ/g$ Hb. So hemoglobin adducts of MABZ were 5 ~ 30 time higher than those of BZ(P<0.003). Above results indicate that work environment assessment didn't detected benzidine and benzidine based dye in ambient air but biological monitoring detected those of hemoglobin adducts. Two group's hemoglobin adducts exposed benzidine dihydrochloride and benzidine based dye were high level but wasn't statistically significant and those were not detected in control group.

• Bulletin of the Korean Chemical Society
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• 제29권8호
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• pp.1583-1586
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• 2008

• Toxicological Research
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• 제14권4호
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• pp.525-533
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• 1998

The covalent interactions of toluenediisocyanate (TDI) with macromolecules were investigated both in vitro and in vivo. In vitro incubations of 2,4- and 2,6-TDI with DNA or proteins resulted in dose-dependent formation of TDI-protein and TDI-DNA adducts. TDI-treated DNA was highly resistant to enzymatic digestion and thermal hydrolysis, but was readily hydrolyzed under acidic conditions by releasing its corresponding toluenediamine (TDA), suggesting that TDI caused the crosslinking of DNA. Reaction of TDI with albumin and globin resulted in the formation of several adducts, and some adducts were formed in blood of TDI-treated rats in a dose-dependent fashion. Administration of TDI to rats resulted also in a dose-dependent binding of TDI to hepatic tissue. Levels of TDI-albumin adducts were 10 times higher than those of TDI-globin adducts; the biological half lives of TDI-albumin and TDI-globin adducts were 1.2 and 12.5 days, respectively. Globin adducts were detected up to 28 days after the treatment. Hepatic TDI protein adducts were persistent for a substantial period whereas the levels of hepatic TDI-DNA adduct were decreased rapidly. These results indicate that the isocyanato group of TDI is not readily hydrolyzed under physiological conditions, is transported to other organs, and is bound to DNA and/or proteins without further metabolic activation. As the adducted products degrade in the body, TDA is released and introduced to the liver. TDA may additionally bind to hepatic tissue after metabolic activation. Thus, the toxic effect of TDI exposure is considered to persist during the lifetime of the adducted biological macromolecules.

• Macromolecular Research
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• 제13권5호
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• pp.427-434
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• 2005

To improve the performance and reduce raw material costs, blocked isocyanates were prepared with mixture of blocking agents in many industries. Three blocked isocyanates (adducts) namely $\varepsilon$-caprolactam/benzotriazole-blocked 4,4'-diphenylmethane diisocyanate (MDI), toluene-2,4-diisocyanate (TDI) and 4,4'-dicyclohexyl-methane diisocyanate ($H_{12}$MDI) were synthesized. Six reference adducts were also prepared by blocking MDI, TDI, and $H_{12}$MDI with $\varepsilon$-caprolactam ($\varepsilon$-CL) or benzotriazole. The reactions were carried out in acetone medium and dibutyltin dilaurate (DBTDL) was used as a catalyst. The progress of the blocking reaction was monitored by IR spectroscopy. De-blocking temperatures (dissociation temperatures) of these adducts were studied using DSC and TGA and the results were correlated. As expected, the thermal analysis data showed that de-blocking temperature of blocked aromatic isocyanates was lower than that of the blocked aliphatic isocyanates. The low de-blocking temperature of blocked aromatic isocyanate could be due to electron withdrawing benzene ring present in the blocked isocyanates. It was also found that benzotriazole-blocked adducts de-blocked at higher temperature compared with $\varepsilon$-CL-blocked adducts.

• 한국환경보건학회지
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• 제30권4호
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• pp.301-307
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• 2004

1,3-butadiene(DB) is a well-established rodent carcinogen, and a probable carcinogen to humans. This study was investigated the formation of hemoglobin adduct in ICR female mice inhaled with BD for 3 weeks (5 hr/day, 5 days/week). Body weights of mice were significantly low from onward day 4 or 9 of exposure comparing the control. Hemoglobin adducts formed by DB exposure were (N-2-hydroxy-3-butenyl) valine (HB Val adduct) and (N-2,3,4-trihydroxy-butyl)valine(THB Val adduct). The levels of HB Val adducts were 1.8, 3.7 and 6.2 pmol/mg globin for the 500 ppm BD inhalation group, and 5.7, 7.4 and 16.0 pmol/mg globin for the 1000 ppm BD inhalation group, when observed on the $1^{st},\;2^{nd},\;and\;3^{rd}$ week after inhalation exposure, respectively. The levels of THBVal adducts were 32.0, 42.0 and 55.0 pmol/mg globin for the 500 ppm DB inhalation group, and 67.8, 72.7 and 83.5 pmol/mg globin for the 1000 ppm BD inhalation group, when observed on the $1^{st},\;2^{nd},\;and\;3^{rd}$ week after inhalation exposure, respectively. Ratios of THBVal and HBVal adducts were higher at earlier exposure period and lower concentration. Ratios on the $1^{st},\;2^{nd},\;and\;3^{rd}$ week were 17.8, 11.4 and 8.87 for the 500 ppm BD inhalation group, and 11.9, 9.8 and 5.2 for the 1000 ppm BD inhalation group, respectively. In conclusion, THB Val and HB Val adducts were the important hemoglobin adducts in ICR female mice inhaled with BD, and the latter was more appropriate biomarker than the other for biological monitoring of BD exposure.

• 한국산업보건학회지
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• 제8권2호
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• pp.289-295
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• 1998

Used gasoline engine oils(UGEO) are carcinogenic in long term studies and capable of increasing the number of carcinogen-DNA adducts in short term studies when dermally applied to mice. The carcinogenic risk of UGEO has been attributed to the concentration of polycyclic aromatic hydrocarbons(PAH) which accumulate in the lubricating system during the combustion of gasoline. When dermally exposed to UGEO, the use of hand cleanser was commonly recommended for removing it. But generally workers who dermally exposed oils, use kerosene as cleaner which make skin trouble. During this study, female mice aged 4-6 weeks were utilized to evaluate the efficiency of kerosene, as solvent-based cleanser, following dermal exposure to UGEO. DNA adduct were detected at skin and lung tissues by using the $^{32}P$-postlabeling method. Washing with cleansers were done at two different interval times following dermal application of UGEO. The total DNA adducts in skin and lung tissues were statistically significantly increased in positive control groups, and of which the total adduct level in skin tissues was statistically significant higher than those in lung tissues(p=0.005). When washing kerosene, the DNA adduct level in skin tissues was statistically significantly decreased(p=0.0001). But DNA adducts in lung tissue was statistically increased(p=0.0039), and that washed at 8hr post exposure was more severly increase(p<0.05). The slope of regression between DNA adducts of lung between skin tissues was 1.0802. In conclusion, skin cleaning with kerosene facilitates passage of carcinogens to the lungs of animals dermally treated with used gasoline engine oils(UGEO).

• Bulletin of the Korean Chemical Society
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• 제23권7호
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• pp.939-940
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• 2002

• Bulletin of the Korean Chemical Society
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• 제33권5호
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• pp.1622-1626
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• 2012

An efficient synthetic method of various 5-hydroxy-3-pyrrolin-2-one derivatives has been developed starting from the MBH adducts. In addition, some synthetic applicability of the prepared 5-hydroxy-3-pyrrolin-2-ones was demonstrated including the synthesis of lactam-fused tetrahydroisoquinolines.

• Toxicological Research
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• 제6권1호
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• pp.63-73
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• 1990

Human exposure to environmental carcinogens can be detected by a number of methods including immunoassay, $^{32}P-postlabeling$ assay, and fluorescence technique. These assays have been applied to measure biological markers of carcinogen-adducts formed with macromolecules such as DNA, RNA and protein. In an attempt to investigate causal relationships between carcinogen exposure and tumor formation, specific carcinogen-adducts have been quantitated from human tissues and body fluids of cancer patients, occupational workers heavily exposed to certain carcinogens, smokers and controls. Carcinogens studied for biological human monitoring include benzo(a)pyrene, aflatoxin B1, UV light, ethylene oxide, 8-methoxypsoralen, 4-aminobiphenyl, vinyl choride, N-nitrosamine, cisplatin and other chemotherapeutic agents. Relevance of human monitoring for cancer research, progress in this field, methods to detect carcinogen-adducts are reviewed here. It is hoped that these approaches will be used for the risk assessment of carcinogen exposure, cancer etiology study and cancer prevention in humans.