Genotoxicity of Streptozotocin

Bolzán, Alejandro D.; Bianchi, Martha S.

doi:10.1016/s1383-5742(02)00044-3

Cited by 342 publications

(240 citation statements)

References 94 publications

Supporting

Mentioning

220

Contrasting

Unclassified

Order By: Relevance

“…STZ treated animals showed altered seminiferous tubules, diminished sperm characteristics, and altered seminal plasma components [8,9]. Although, STZ in various animal studies demonstrated as a successful model for diabetes, there are concerns about potential toxic effects of this chemical due to its carcinogenic and mutagenic property [10,11]. It remains unclear whether the responses in experimental model are due to hyperglycemia or streptozotocin itself.…”

Section: Introductionmentioning

confidence: 99%

Germ cell abnormalities in streptozotocin induced diabetic mice do not correlate with blood glucose level

Bose

Adiga

D’Souza

et al. 2012

J Assist Reprod Genet

View full text Add to dashboard Cite

Purpose To assess the effect of streptozotocin induced hyperglycemia on germ cell integrity, DNA ploidy and methylation status for a period of two spermatogenesis cycles in adult male Swiss albino mice. Methods Streptozotocin injected mice were monitored for hyperglycemia at a regular interval for a period of 36 and 72 days. The DNA integrity in epididymal spermatozoa was determined by the comet assay. Flow cytometric analysis was done in germ cells to assess the DNA ploidy. The global methylation analysis in germ cells was done by 5-methyl cytosine immunostaining.Results Streptozotocin administration successfully resulted in hyperglycemic response which significantly affected serum testosterone level, sperm DNA integrity and DNA ploidy at the end of 36 days. However, no changes were observed in either epididymal sperm concentration or germ cell methylation status. In contrast, at the end of 76 days, although serum testosterone level, sperm DNA integrity and DNA ploidy status were unperturbed significantly in hyperglycemic group, the epididymal sperm concentration and methylation status of preleptotene/zygotene cells were significantly altered. Importantly, an attempt to find out the association between the blood glucose levels and the abnormalities in hyperglycemic group failed to demonstrate any correlation. Conclusions The germ cell abnormalities observed in hyperglycemic group could be interpreted as a primary effect of streptozotocin and not due to hyperglycemia. Our results call for further evaluation of streptozotocin before its application to study the hyperglycemic responses on male germ cells.

show abstract

Section: Introductionmentioning

confidence: 99%

Germ cell abnormalities in streptozotocin induced diabetic mice do not correlate with blood glucose level

Bose

Adiga

D’Souza

et al. 2012

J Assist Reprod Genet

View full text Add to dashboard Cite

show abstract

“…Our previous work has indeed suggested that susceptibility of the NOD mouse to HDS-diabetes was related to a peculiarity of its pancreatic beta cells, which could be also involved in the pathogenesis of Type 1 diabetes [6]. Moreover, some of the known mechanisms of STZ toxicity, such as NO and free radical release [7,9], are also implicated in autoimmune destruction of islets of Langerhans [10,25]. In the ALR/Lt mouse, resistant to alloxan-induced diabetes, a locus in chromosome 3 has indeed been recently linked both to reduction of superoxide production by neutrophils and to spontaneous diabetes resistance [26], suggesting that a gene involved in resistance to alloxan-induced diabetes could also protect against autoimmune diabetes.…”

Section: Discussionmentioning

confidence: 98%

“…In contrast to multiple low doses of STZ (MLDS), which eventually induce an immune-mediated diabetes [4,5], a high dose of STZ (HDS) mediates diabetes by exercising only a direct toxicity on beta cells [6]. Although many researchers have studied STZ pancreatotoxicity, the exact mechanisms remain unknown [5,7]. On the one hand, STZ is a potent alkylating agent which directly damages DNA [7,8].…”

mentioning

confidence: 99%

“…Although many researchers have studied STZ pancreatotoxicity, the exact mechanisms remain unknown [5,7]. On the one hand, STZ is a potent alkylating agent which directly damages DNA [7,8]. On the other hand, decomposition of STZ might generate free radicals such as nitric Streptozotocin (STZ) was first identified in 1956 from cultures of streptomyces achromogenes [1].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Genetic control of non obese diabetic mice susceptibility to high-dose streptozotocin-induced diabetes

et al. 2003

View full text Add to dashboard Cite

Aims/hypothesis. Streptozotocin is a monofunctional alkylating agent that induces diabetes in a large variety of mammals. While multiple low doses of streptozotocin induce immune-mediated diabetes, a single high dose of streptozotocin causes a strictly toxic diabetes. Among mouse strains, non-obese diabetic (NOD) mice are characterized by an extreme susceptibility to high dose of streptozotocin-induced diabetes whereas C3H/Or mice are particularly resistant. We hypothesized that NOD genes involved in high dose streptozotocin-induced diabetes could be also involved in the autoimmune destruction of pancreatic beta cells that characterizes this mouse strain which is a model of Type 1 diabetes. Methods. We carried out a whole genome linkage scan on a population of (C3H/Or × NOD) × NOD backcross 1 mice in order to identify the genetic loci involved in NOD susceptibility to high dose of streptozotocin-induced diabetes.Results. Two loci, in chromosome 9 (D9Mit135 marker, 48 cM) and in chromosome 11 (D11Mit286 marker, 52 cM), were associated with NOD susceptibility to high dose streptozotocin-induced diabetes, the latter being co-localized with the autoimmune diabetes-predisposing idd4 locus. Moreover, we report here that C57BL/6 mice deficient in Nitric Oxide Synthase 2 were as sensitive as wild-type C57BL/6 mice to high dose streptozotocin-induced diabetes. Conclusion/interpretation. Although the Nitric Oxide Synthase 2 (Nos2) gene, localized at 45.6 cM in chromosome 11, is a good candidate gene, our results suggest that Nitric Oxide Synthase 2 activation might not be a crucial event for streptozotocin-induced destruction of pancreatic beta cells. [Diabetologia (2003[Diabetologia ( ) 46:1291[Diabetologia ( -1295 Keywords Non-obese diabetic mouse, diabetes, autoimmune, streptozotocin, pancreatic beta cells, genetic susceptibility, nitric-oxide synthase, C3H, C57BL/6, idd4, genome scan.

show abstract

“…Moreover, streptozotocin is highly genotoxic, leading to the production of DNA strand breaks. A single administration can also induce tumours in rat kidney, liver and pancreas [18], precluding long-term experiments required for analyses of beta stem cells. Therefore, alternative hyperglycaemic mouse models that do not require chemical beta cell destruction to render the immunodeficient host hyperglycaemic are of great interest as recipients of human islets and human beta cell stem and progenitor cells.…”

Section: Introductionmentioning

confidence: 99%

A new immunodeficient hyperglycaemic mouse model based on the Ins2 Akita mutation for analyses of human islet and beta stem and progenitor cell function

et al. 2008

View full text Add to dashboard Cite

Aims/hypothesis To develop and validate a new immunodeficient mouse strain that spontaneously develops a nonautoimmune hyperglycaemia to serve as a diabetic host for human islets and human beta stem and progenitor cells without the need for induction of hyperglycaemia by toxic chemicals with their associated side effects. Methods We generated and characterised a new strain of immunodeficient spontaneously hyperglycaemic mice, the NOD-Rag1 null Prf1 null Ins2 Akita strain and compared this strain with the NOD-scid Il2rγ null (also known as Il2rg) immunodeficient strain rendered hyperglycaemic by administration of a single dose of streptozotocin. Hyperglycaemic mice were transplanted with human islets ranging from 1,000 to 4,000 islet equivalents (IEQ) and were monitored for normalisation of blood glucose levels. Results NOD-Rag1 null Prf1 null Ins2 Akita mice developed spontaneous hyperglycaemia, similar to Ins2 Akita -harbouring strains of immunocompetent mice. Histological examination of islets in the host pancreas validated the spontaneous loss of beta cell mass in the absence of mononuclear cell infiltration. Human islets transplanted into spontaneously diabetic NOD-Rag1 null Prf1 null Ins2 Akita and chemically diabetic NOD-scid Il2rγ null mice resulted in a return to euglycaemia that occurred with transplantation of similar beta cell masses. Conclusions/interpretation The NOD-Rag1 null Prf1 null Ins2 Akita mouse is the first immunodeficient, spontaneously hyperglycaemic mouse strain described that is based on the Ins2 Akita mutation. This strain is suitable as hosts for human islet and human beta stem and progenitor cell transplantation in the absence of the need for pharmacological induction of diabetes. This strain of mice also has low levels of innate immunity and can be engrafted with a human immune system for the study of human islet allograft rejection.

show abstract

Genotoxicity of Streptozotocin

Cited by 342 publications

References 94 publications

Germ cell abnormalities in streptozotocin induced diabetic mice do not correlate with blood glucose level

Germ cell abnormalities in streptozotocin induced diabetic mice do not correlate with blood glucose level

Genetic control of non obese diabetic mice susceptibility to high-dose streptozotocin-induced diabetes

A new immunodeficient hyperglycaemic mouse model based on the Ins2 Akita mutation for analyses of human islet and beta stem and progenitor cell function

Contact Info

Product

Resources

About