PMID- 8642054
OWN - NLM
STAT- MEDLINE
DCOM- 19960718
LR  - 20151119
IS  - 0270-4145 (Print)
IS  - 0270-4145 (Linking)
VI  - 15
IP  - 3
DP  - 1995 Jul-Sep
TI  - Effects of caffeine and nicotine administration on growth and ossification of the 
      ICR mouse fetus.
PG  - 146-56
AB  - The objective of this study was to determine how fetal effects are altered when 
      nicotine (N) and caffeine (CA) are administered concurrently at dosages that 
      individually produce minimal effects to the fetus. Female ICR mice were bred 
      overnight and were assigned to four groups: CA (125 mg/kg), N (12mg/kg), CA plus 
      N (125 mg/kg plus 12 mg/kg, respectively) treated, and control (distilled water) 
      groups. Dams were intubated with these dosages three times daily during 
      gestational days (GD) 6-18 and were euthanized on GD 18. Live fetuses were sexed, 
      weighed, and examined for external malformations. One-half of the fetuses were 
      fixed in 10% formalin and examined for internal malformations using Wilson's 
      method. The remaining half was fixed in 95% ethanol (ETOH), stained, and cleared 
      (Inouye's method) for skeletal examinations. Ossification was assessed by staging 
      and measuring craniofacial bones, and counting ossification centra in sternbrae 
      and in cervical and sacrococcygeal vertebrae. Data were analyzed by analysis of 
      variance (ANOVA) followed by Student-Newman-Keuls post-hoc tests set at p < .05 
      significance level. The litter was used as the unit of measure and the ANOVA main 
      effects were CA, N, and an interaction term (CA+N). In comparison to controls, CA 
      treatment resulted in reduced bone measurements or reduced ossification scores in 
      5 of the 19 parameters examined, whereas for N only five parameters were 
      significant. The main effects for interaction of CA+N were significant for seven 
      parameters measured. Although it is difficult to assign the specific type of drug 
      interaction that occurred because results were not completely consistent for all 
      parameters measured, it may be concluded that in most parameters measured both CA 
      and CA+N were different from controls, but CA was not different from CA+N. Under 
      the experimental conditions of this study, we found that of the two drugs, 
      caffeine had a significantly greater effect on fetal growth and ossification than 
      nicotine.
FAU - Leblebicioglu-Bekcioglu, B
AU  - Leblebicioglu-Bekcioglu B
AD  - Ohio State University, College of Dentistry, Department of Oral Biology, Columbus 
      43210, USA.
FAU - Paulson, R B
AU  - Paulson RB
FAU - Paulson, J O
AU  - Paulson JO
FAU - Sucheston, M E
AU  - Sucheston ME
FAU - Shanfeld, J
AU  - Shanfeld J
FAU - Bradway, S D
AU  - Bradway SD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Denmark
TA  - J Craniofac Genet Dev Biol
JT  - Journal of craniofacial genetics and developmental biology
JID - 8109845
RN  - 3G6A5W338E (Caffeine)
RN  - 6M3C89ZY6R (Nicotine)
SB  - IM
MH  - Animals
MH  - Bone and Bones/abnormalities/drug effects/*embryology
MH  - Caffeine/blood/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Embryonic and Fetal Development/*drug effects
MH  - Extremities/embryology
MH  - Female
MH  - Fetal Death
MH  - Limb Deformities, Congenital
MH  - Litter Size
MH  - Maternal Age
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Nicotine/blood/*pharmacology
MH  - Organ Size
MH  - Placenta/anatomy & histology
EDAT- 1995/07/01 00:00
MHDA- 1995/07/01 00:01
CRDT- 1995/07/01 00:00
PHST- 1995/07/01 00:00 [pubmed]
PHST- 1995/07/01 00:01 [medline]
PHST- 1995/07/01 00:00 [entrez]
PST - ppublish
SO  - J Craniofac Genet Dev Biol. 1995 Jul-Sep;15(3):146-56.