Indications of repair of radon-induced chromosome damage in human lymphocytes: an adaptive response induced by low doses of X-rays.

Naturally occurring radon is a relatively ubiquitous environmental carcinogen to which large numbers of people can be exposed over their lifetimes. The accumulation of radon in homes, therefore, has led to a large program to determine the effects of the densely ionizing alpha particles that are produced when radon decays. In human lymphocytes, low doses of X-rays can decrease the number of chromatid deletions induced by subsequent high doses of clastogens. This has been attributed to the induction of a repair mechanism by the low-dose exposures. Historically, chromosome aberrations induced by radon have been considered to be relatively irreparable. The present experiments, however, show that if human peripheral blood lymphocytes are irradiated with low doses of X-rays (2 cGy) at 48 hr of culture, before being exposed to radon at 72 hr of culture, the yield of chromatid deletions induced by radon is decreased by a factor of two. Furthermore, the numbers of aberrations per cell do not follow a Poisson distribution but are overdispersed, as might be expected because high-linear energy transfer (high LET) alpha particles have a high relative biological effectiveness compared to low-LET radiations such as X-rays or gamma rays. Pretreatment with a low dose of X-rays decreases the overdispersion and leads to a greater proportion of the cells having no aberrations, or lower numbers of aberrations, than is the case in cells exposed to radon alone.(ABSTRACT TRUNCATED AT 250 WORDS

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Genetic Toxicity of Sulfur Mustard (HD) in Chinese Hamster Ovary Cells Final Report

The cytotoxic, clastogenic and mutagenic effects of sulfur nustard in Chinese hamster ovary cells are described in this reoort. The cytotoxicity data indicate that micromolar amounts of HC are highly toxic in microrolar amounts. Chromosone aberration frequencies increased in a dose-dependent manner over a dose range of 0. 5 to 1.0 {micro}m and SCE increased in a dose-dependent fashion in the dose range of 0.0625 to 0.25 {micro}M. Mutation induction at the HGPRT locus was sporadic, but the majority of the exoosures resulted in mutation frequencies which were 1.2 to 4.3 fold higher than the spontaneous frequencies

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Genetic Toxicity of Sulfur Mustard (HD) in Chinese Hamster Ovary Cells Final Report

The cytotoxic, clastogenic and mutagenic effects of sulfur nustard in Chinese hamster ovary cells are described in this reoort. The cytotoxicity data indicate that micromolar amounts of HC are highly toxic in microrolar amounts. Chromosone aberration frequencies increased in a dose-dependent manner over a dose range of 0. 5 to 1.0 {micro}m and SCE increased in a dose-dependent fashion in the dose range of 0.0625 to 0.25 {micro}M. Mutation induction at the HGPRT locus was sporadic, but the majority of the exoosures resulted in mutation frequencies which were 1.2 to 4.3 fold higher than the spontaneous frequencies

Toxicology Studies of Lewisite and Sulfur Mustard Agents: Genetic Toxicity of Lewisite (L) In Chinese Hamster Ovary Cells

The cytotoxic clastogenic and mutagenic effects of the arsenic containing vesicant, Lewisite (L) [dichloro(2-chlorovinyl) arsine], have been investigated using Chinese hamster ovary cells. One hour exposures to Lewisite were cytotoxic in uM amounts. The cell survival response yields a D37 of 0.6 uM and an extrapolation number of 2.5. The mutagenic response at the hypoxantnine-guanine phosporibosyl transferase (HGPRT) locus was sporadic and not significantly greater than control values when cells were exposed over a range of 0.125 to2.0 uM. Sister chromatid exchange (SCE) induction, a measure of chromosomal rearrangement, was weakly positive over a range of 0.25 to 1.0 uM but the values were not significantly greater than the control response. Chromosomal aberrations were induced at 0.75 and 1.0 UMin one experiment and 0.5 and 0.75 uM in another experiment. The Induced values were significantly greater than the control values. Lewisite appears to be cytotoxic and clastogenic in our investigations but SCE and mutation at the HGPRT locus are not significantly greater than control values. Lewisita toxicity was in some ways similar to radiomimetic chemicals such as bleomycin

Re-visiting the Protamine-2 locus: deletion, but not haploinsufficiency, renders male mice infertile

Protamines are arginine-rich DNA-binding proteins that replace histones in elongating spermatids. This leads to hypercondensation of chromatin and ensures physiological sperm morphology, thereby protecting DNA integrity. In mice and humans, two protamines, protamine-1 (Prm1) and protamine-2 (Prm2) are expressed in a species-specific ratio. In humans, alterations of this PRM1/PRM2 ratio is associated with subfertility. By applying CRISPR/Cas9 mediated gene-editing in oocytes, we established Prm2-deficient mice. Surprisingly, heterozygous males remained fertile with sperm displaying normal head morphology and motility. In Prm2-deficient sperm, however, DNA-hypercondensation and acrosome formation was severely impaired. Further, the sperm displayed severe membrane defects resulting in immotility. Thus, lack of Prm2 leads not only to impaired histone to protamine exchange and disturbed DNA-hypercondensation, but also to severe membrane defects resulting in immotility. Interestingly, previous attempts using a regular gene-targeting approach failed to establish Prm2-deficient mice. This was due to the fact that already chimeric animals generated with Prm2+/− ES cells were sterile. However, the Prm2-deficient mouse lines established here clearly demonstrate that mice tolerate loss of one Prm2 allele. As such they present an ideal model for further studies on protamine function and chromatin organization in murine sperm

THIOMETALATO COMPLEXES - ELECTRONIC-STRUCTURES AND THE RELATION TO THEIR CHEMICAL AND PHYSICAL-PROPERTIES

JOSTES R, Müller A. THIOMETALATO COMPLEXES - ELECTRONIC-STRUCTURES AND THE RELATION TO THEIR CHEMICAL AND PHYSICAL-PROPERTIES. THEOCHEM-JOURNAL OF MOLECULAR STRUCTURE. 1988;41(3-4):211-247

TRINUCLEAR CLUSTERS OF THE EARLY TRANSITION-ELEMENTS

Müller A, JOSTES R, COTTON FA. TRINUCLEAR CLUSTERS OF THE EARLY TRANSITION-ELEMENTS. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH. 1980;19(11):875-882

DELOCALIZED MOLECULAR-ORBITALS IN THE TRIMETALLIC THIOHETEROANION [S2WS2COS2SW2]2- - SPECTROSCOPIC AND CYCLIC VOLTAMMETRIC RESULTS

Müller A, JOSTES R, FLEMMING V, POTTHAST R. DELOCALIZED MOLECULAR-ORBITALS IN THE TRIMETALLIC THIOHETEROANION [S2WS2COS2SW2]2- - SPECTROSCOPIC AND CYCLIC VOLTAMMETRIC RESULTS. INORGANICA CHIMICA ACTA-LETTERS. 1980;44(1):L33-L35

ELECTRONIC-STRUCTURE AND SPECTRA OF OXOTHIOMETALATES MO4-NSN(2-)(M=MO, W, N=0-4)

Jostes R, Müller A, Diemann E. ELECTRONIC-STRUCTURE AND SPECTRA OF OXOTHIOMETALATES MO4-NSN(2-)(M=MO, W, N=0-4). THEOCHEM-JOURNAL OF MOLECULAR STRUCTURE. 1986;30(3-4):311-328

TRANSITION-METAL THIOMETALATES - PROPERTIES AND SIGNIFICANCE IN COMPLEX AND BIOINORGANIC CHEMISTRY

Müller A, Diemann E, JOSTES R, Bögge H. TRANSITION-METAL THIOMETALATES - PROPERTIES AND SIGNIFICANCE IN COMPLEX AND BIOINORGANIC CHEMISTRY. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH. 1981;20(11):934-955