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Use of in vivo/in vitro unscheduled DNA synthesis for identification of organ-specific carcinogens.
Crit Rev Toxicol. 1987; 17(3):245-77.CR

Abstract

There are still only a few in vivo short-term assay methods for predicting potential organ-specific carcinogens and mutagens in mammals, although such methods are required for evaluating the in vivo effects of in vitro mutagens. In the in vivo/in vitro UDS assay methods described here, chemicals are given to experimental animals and induction of UDS in target organs is determined by in vitro organ culture or primary cell culture in the presence of [3H]dThd. Incorporation of [3H]dThd into DNA is measured with a liquid scintillation counter or by autoradiography. These methods have now been applied to the glandular stomach, forestomach, colon, liver, kidney, pancreas, tracheal epithelium, nasal epithelium, and spermatocytes. With minor modifications, they may also be applied to other organs. The present review shows that induction of UDS in various organs correlated well with the induction of cancer in these organs. The present authors have used the present methods to identify some potential organ-specific mutagens and carcinogens in mammals. The present authors found that three dicarbonyl compounds, glyoxal, methylglyoxal, and diacetyl, induced apparent UDS and TDS in the glandular stomach, and other groups found that 2-NT, MA6BT, and CNEt6BT induced UDS in the liver. These in vivo/in vitro UDS assays are better than in vitro UDS assay for identification of potential organ-specific mutagens and carcinogens in mammals and are especially useful for identifying potential mutagens and carcinogens that are specific for certain organs, such as the stomach, liver, and kidney. They are also useful for examining the potential mutagenicities and carcinogenicities of carcinogen analogs. However, these methods are not suitable for general in vivo screening because they are not yet available for all organs. A further advantage of the methods is that they can be used to examine larger numbers of animals at one time than other methods for detecting DNA damage, such as alkaline elution or alkaline sucrose density gradient centrifugation. Glyoxal enhanced cancer induction in the glandular stomach by the administration of a limited amount of MNNG and then glyoxal afterward in the two-stage stomach carcinogenesis.

Authors

No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

3556021

Citation

Furihata, C, and T Matsushima. "Use of in Vivo/in Vitro Unscheduled DNA Synthesis for Identification of Organ-specific Carcinogens." Critical Reviews in Toxicology, vol. 17, no. 3, 1987, pp. 245-77.
Furihata C, Matsushima T. Use of in vivo/in vitro unscheduled DNA synthesis for identification of organ-specific carcinogens. Crit Rev Toxicol. 1987;17(3):245-77.
Furihata, C., & Matsushima, T. (1987). Use of in vivo/in vitro unscheduled DNA synthesis for identification of organ-specific carcinogens. Critical Reviews in Toxicology, 17(3), 245-77.
Furihata C, Matsushima T. Use of in Vivo/in Vitro Unscheduled DNA Synthesis for Identification of Organ-specific Carcinogens. Crit Rev Toxicol. 1987;17(3):245-77. PubMed PMID: 3556021.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Use of in vivo/in vitro unscheduled DNA synthesis for identification of organ-specific carcinogens. AU - Furihata,C, AU - Matsushima,T, PY - 1987/1/1/pubmed PY - 1987/1/1/medline PY - 1987/1/1/entrez SP - 245 EP - 77 JF - Critical reviews in toxicology JO - Crit Rev Toxicol VL - 17 IS - 3 N2 - There are still only a few in vivo short-term assay methods for predicting potential organ-specific carcinogens and mutagens in mammals, although such methods are required for evaluating the in vivo effects of in vitro mutagens. In the in vivo/in vitro UDS assay methods described here, chemicals are given to experimental animals and induction of UDS in target organs is determined by in vitro organ culture or primary cell culture in the presence of [3H]dThd. Incorporation of [3H]dThd into DNA is measured with a liquid scintillation counter or by autoradiography. These methods have now been applied to the glandular stomach, forestomach, colon, liver, kidney, pancreas, tracheal epithelium, nasal epithelium, and spermatocytes. With minor modifications, they may also be applied to other organs. The present review shows that induction of UDS in various organs correlated well with the induction of cancer in these organs. The present authors have used the present methods to identify some potential organ-specific mutagens and carcinogens in mammals. The present authors found that three dicarbonyl compounds, glyoxal, methylglyoxal, and diacetyl, induced apparent UDS and TDS in the glandular stomach, and other groups found that 2-NT, MA6BT, and CNEt6BT induced UDS in the liver. These in vivo/in vitro UDS assays are better than in vitro UDS assay for identification of potential organ-specific mutagens and carcinogens in mammals and are especially useful for identifying potential mutagens and carcinogens that are specific for certain organs, such as the stomach, liver, and kidney. They are also useful for examining the potential mutagenicities and carcinogenicities of carcinogen analogs. However, these methods are not suitable for general in vivo screening because they are not yet available for all organs. A further advantage of the methods is that they can be used to examine larger numbers of animals at one time than other methods for detecting DNA damage, such as alkaline elution or alkaline sucrose density gradient centrifugation. Glyoxal enhanced cancer induction in the glandular stomach by the administration of a limited amount of MNNG and then glyoxal afterward in the two-stage stomach carcinogenesis. SN - 1040-8444 UR - https://www.unboundmedicine.com/medline/citation/3556021/Use_of_in_vivo/in_vitro_unscheduled_DNA_synthesis_for_identification_of_organ_specific_carcinogens_ L2 - https://www.tandfonline.com/doi/full/10.3109/10408448709071210 DB - PRIME DP - Unbound Medicine ER -