Molecular dosimetry

Potter, D., T.M. Clarius, A.S. Wright, and W.P. Watson. 1994. Molecular dosimetry of DNA adducts in rainbow trout (Oncorhynchus mykiss) exposed to benzo[a]pyrene by different routes. Arch. Toxicol. 69 1-7. 

Studies investigating the bioavailability of P.Y.17 in rats, applied not only orally but also by inhalation, in no case showed the presence of any cleavage product of the pigment (e.g., 3,3-dichlorobenzidine or metabolites) in the urine or blood of the animals [31]. Similar studies were carried out with P.Y.13 and 174 [32], Recently the non-bioavailability of 3,3 -dichlorobenzidine from P.Y.13 and P.Y.17 was confirmed by means of molecular dosimetry for hemoglobin and DNA adducts [33]. 

Sagelsdorff P, Haengii R, Heuberger B, et al. 1996. Lack of bioavailability of dichlorobenzidine from diarylide azo pigments Molecular dosimetry for hemoglobin and DNA adduets. Careinogenesis 17(3) 507-514. 

Bodell WJ. Molecular dosimetry of sister ehromatid exehange induetion in 9L cells treated with 6-thioguanine. Mutagenesis 1991 6 175-177. 

Steiner, S., Crane, A.E. Watson, W.P (1992a) Molecular dosimetry of DNA adducts in C3H mice treated with glycidaldehyde. Carcinogenesis, 13, 119-124... 

Abbondandolo, A., Dogliotti, E., Lohman, P.H.M. Brerends, F. (1982) Molecular dosimetry of DNA damage caused by alkylation. I. Single-strand breaks induced by ethylating agents in cultured mammalian cells in relation to survival. Mutat. Res., 92,361-377... 

Skipper P., and J. Groopman. 1991. Molecular Dosimetry and Human Cancer Analytical, epidemiological, and social considerations. Boca Raton, Fla. CRC Press. 

Research in better mutation-detection systems and in molecular dosimetry is progressing rapidly, and it is likely that better procedures for mutagen detection and risk assessment will be forthcoming. This means that some of our recommended testing procedures cure likely to be superseded in a few years. 

Although the use of simple test systems to predict genetic effects in whole mammals is desirable, comparison of dosages in submammalian systems with human exposure is extremely complex. The nature of the exposure, cellular toxicity, and units of measurement differ markedly from one type of organism to another. Molecular dosimetry that measures adducts in DNA is promising,1-3 237-239 jjUt the ability to relate exposures in short-term test systems, including mammalian cell cultures, to human risks is primitive. There are much better grounds for qualitative than for quantitative extrapolation. 

Molecular dosimetry offers a premising approach for more precise and reproducible dose measurement, thereby... 

Molecular dosimetry cam be used to create a net of chemical bridges among test mammals and between mammals and lower eukaryotic systems. This can be illustrated with a simple example ... 

In this example, D is some observed end point in the mammal—specific-locus mutation rate, skeletal anomalies, cataracts, or heritable chromosomal damage. The values for D and E are assumed to be the same, although our confidence in the extrapolation would be increased if the observations in D involved several strains of several mammals. There is some possibility of direct dosimetry in man. With molecular dosimetry, the ENA damage in A and B can be measured in the same way. This corrects for differences in mutagen metabolism and mutation processes in the two organisms. B is measured directly in the spermatogonia or oocytes. The mutational end point, C, is whatever is most appropriate for the particular test organism. 

Various methods for molecular dosimetry have been proposed and developed, but they are not practical for routine use and have not been validated. A dosimetric method that could be applied directly to humans would be particularly valuable. 

Aaron/ C.S. Molecular dosimetry of chemical mutagens selection of appropriate target molecules for determining molecular dose to the germ line. Mutat. Res. 38 303-310, 1976. 

Aaron, C.S., and W.R. Lee. Molecular dosimetry of the mutagen ethyl methanesulfonate in Drosophila melanogaster spermatozoa linear relation of DNA alkylation per sperm cell (dose) to sex-linked recessive lethals. Mutat. Res. 49 27-44, 1978. 

Aaron, C.S., A.A. Van Zeeland, G.R. Mohn, A.T. Natarajan, A.G.A.C. Knaap, A.D. Tates, and B.W. Glickman. Molecular dosimetry of the chemical mutagen ethyl methanesulfonate quantitative comparison of mutation induction in Escherichia coli, V79 Chinese hamster cells and L5178Y mouse lymphoma cells, and some cytological results in vitro and in vivo. Mutat. Res. 69 201-216, 1980. 

Sega, G.A. Molecular dosimetry of chemical mutagens. Measurement of molecular dose and ENA repair in mammalian germ cells. Mutat. Res. 38 317-326, 1976. 

Bodell WY, Pathak DN, Levay G, et al. 1996. Investigation of the DNA adducts formed in B6C3F1 mice treated with benzene Implications for molecular dosimetry. Environ Health Perspect 104 (Suppl 6) 1189-1193. 

C. P. Wild et al, Molecular dosimetry of aflatoxin exposure contribution to understanding multifactorial etiopathogenesis of primary hepatocellular carcinoma with particular reference to hepatitis B virus . Environmental Health Perspectives, 99 (1993), 115-22. 

Boucheron JA, Richardson FC, Morgan PH, Swenberg JA. 1987. Molecular dosimetry of 04-ethyldeoxythymidine in rats continuously exposed to diethylni-trosamine. Cancer Res. 47 1577-81... 

Belinsky SA, Walker VE, Maronpot RR, Swenberg JA, Anderson MW. 1987. Molecular dosimetry of DNA adduct formation and cell toxicity in rat nasal mucosa following exposure to the tobacco specific nitrosamine 4-(N-methyl-N-nit-rosami no)-1 -(3-pyridyl)-1 -butanone and their relationship to induction of neoplasia. Cancer Res. 47 6058-65... 

Sabbioni G. Hemoglobin binding of aromatic amines molecular dosimetry and quantitative structure-activity relationships for jV-oxidation. Environ Health Per-spect 1993 99 213-6. 

Bailey, G.S., R. Dashwood, P.M. Loveland, C. Pereira and J.D. Hendricks. Molecular dosimetry in fish quantitative target organ DNA adduction and hepatocarcinogenicity for four aflatoxins by two exposure routes in rainbow trout. Mutat. Res. Fund. Mol. Mech. Mutagen. 399 233-244, 1998. 

Wiencke JK, McDowell ML, Bodell WJ. 1990. Molecular dosimetry of DNA adducts and sister chromatid exchanges in human lymphocytes treated with benzo(a)pyrene. Carcinogenesis 11 (9) 1497-1502. 

Roebuck BD, Liu YL, Rogers AE, Groopman JD, Kensler TW. Protection against aflatoxin Bl-induced hepatocarcinogenesis in F344 rats by 5-(2-pyrazmyl)-4-methyl-l,2-dithiole-3-thione (oltipraz) predictive role for short-term molecular dosimetry. Cancer Res 1991 51 5501-5506. 

Using epidemiological methods, the relationship between aflatoxln exposure and human liver cancer has been hindered by inadequate data on aflatoxln consumption, excretion, metabolism, and the general poor quality of world-wide cancer morbidity and mortality statistics. Molecular dosimetry methods are needed to help accurately assess an individual s exposure to aflatoxins. This is especially important because of the recent reclassification by the... 

---