K. De Ruyck

Microsatellite Polymorphisms in DNA Repair Genes XRCC1, XRCC3 and XRCC5 in Patients with Gynecological Tumors: Association with Late Clinical Radiosensitivity and Cancer Incidence

Abstract De Ruyck, K., Wilding, C. S., Van Eijkeren, M., Morthier, R., Tawn, E. J. and Thierens, H. Microsatellite Polymorphisms in DNA Repair Genes XRCC1, XRCC3 and XRCC5 in Patients with Gynecological Tumors: Association with Late Clinical Radiosensitivity and Cancer Incidence. Radiat. Res. 164, 237–244 (2005). This study investigates the association of microsatellite polymorphisms in XRCC1, XRCC3 and XRCC5 with the development of late radiation-induced radiotherapy reactions and examines the correlation between these microsatellites and cancer incidence. Sixty-two women with cervical or endometrial cancer treated with radiotherapy were included in the study. According to the CTCAEv3.0 scale, 22 patients showed late adverse radiotherapy reactions (grade 2 or more). PCR on lymphocyte DNA followed by automated fragment analysis was performed to examine the number of tandem repeat units at each locus. No significant association was found between the repeat length at any of the microsatellites in XRCC1, XRCC3 or XRCC5 and the incidence of late radiotherapy complications. Since higher odds ratios (ORs) were found for the rare XRCC1 [AC]11 and [AC]21 repeats (OR = 2.65, P = 0.325 and OR = 8.67, P = 0.093, respectively), the possible involvement of these small and large repeats in clinical radiosensitivity cannot be completely ruled out. When specific numbers of repeats were examined, no significant correlation was found between the microsatellite repeat length in XRCC1 and XRCC5 and cancer incidence. A weak correlation between XRCC3 [AC]16 homozygotes and cancer incidence was found (OR = 2.56, P = 0.055). A large-scale multicenter study of cancer patients with a high number of radiosensitive individuals is needed to clarify the value of rare polymorphic microsatellite repeats in XRCC1 and XRCC3 as a biomarker of clinical radiosensitivity or increased cancer risk.

Chromosomal radiosensitivity in head and neck cancer patients: evidence for genetic predisposition?

The association between chromosomal radiosensitivity and genetic predisposition to head and neck cancer was investigated in this study. In all, 101 head and neck cancer patients and 75 healthy control individuals were included in the study. The G2 assay was used to measure chromosomal radiosensitivity. The results demonstrated that head and neck cancer patients had a statistically higher number of radiation-induced chromatid breaks than controls, with mean values of 1.23 and 1.10 breaks per cell, respectively (P<0.001). Using the 90th percentile of the G2 scores of the healthy individuals as a cutoff value for chromosomal radiosensitivity, 26% of the cancer patients were radiosensitive compared with 9% of the healthy controls (P=0.008). The mean number of radiation-induced chromatid breaks and the proportion of radiosensitive individuals were highest for oral cavity cancer patients (1.26 breaks per cell, 38%) and pharynx cancer patients (1.27 breaks per cell, 35%). The difference between patients and controls was most pronounced in the lower age group (⩽50 years, 1.32 breaks per cell, 38%) and in the non- and light smoking patient group (⩽10 pack-years, 1.28 breaks per cell, 46%). In conclusion, enhanced chromosomal radiosensitivity is a marker of genetic predisposition to head and neck cancer, and the genetic contribution is highest for oral cavity and pharynx cancer patients and for early onset and non- and light smoking patients.

Effect of changes in lipid classes during wilting and ensiling of red clover using two silage additives on in vitro ruminal biohydrogenation

Although forage lipid is generally rich in polyunsaturated fatty acids (PUFA), recovery of these fatty acids (FA) in milk and meat of ruminant origin is generally low, due to microbial biohydrogenation (BH) taking place in the rumen. Since lipolysis is a prerequisite for BH, the latter process is expected to be enhanced when (conserved) forages contain lower levels of esterified FA (particularly polar lipids; PL). However, this was not observed in former studies with red clover ( Trifolium pratense L.). Furthermore, red clover inclusion in the herbivores diet was associated with decreased rumen BH as compared with other forages. Differences in plant lipase activity during wilting and ensiling has been attributed to changes in disappearance from the PL fraction, but a potential role of microbial lipases in silo has not yet been elucidated. Therefore, the aims of the present study were to assess whether BH of red clover FA is linked with PL levels of the (conserved) starting material and to clarify the possible role of in silo microbial activity on PL disappearance. In order to obtain sufficient variation in forage PL and microbial activity, laboratory-scale silages were made by wilting and ensiling damaged or undamaged red clover using molasses or formic acid as ensiling additive, while perennial ryegrass ( Lolium perenne L.) was used as a control. Distribution of lipids within three lipid fractions (PL, free FA and neutral lipids) in forages was determined and BH calculated after 24 h in vitro rumen incubation. Results indicated microbial lipases in silages did not enhance FA disappearance from the PL fraction. A gradual decrease of FA in the PL fraction upon conservation was found, both in red clover and ryegrass, irrespective of the degree of damage. In red clover PL losses started from the wilting phase, while substantial PL disappearance from ryegrass only started upon ensiling. Proportions of PUFA remaining in the PL fraction after wilting and ensiling of red clover were positively correlated with PUFA BH, while this effect was not observed for ryegrass. Red clover PUFA seemed to be partially protected against ruminal BH, while disappearance of FA from the PL fraction did not seem to be hampered. Results indicated the encapsulation mechanism as a consequence of protein-bound phenol formation induced by polyphenol oxidase is still the most probable hypothesis to explain red clovers increased flow of PUFA across the rumen.